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| Therapy Name | Lorlatinib |
| Synonyms | |
| Therapy Description |
Lorbrena (lorlatinib) is a small molecule inhibitor of Alk and Ros1 fusion proteins, which may result in suppression of Alk and Ros1-mediated signaling thereby inhibiting cell growth and causing tumor regression (PMID: 26144315). Lorbrena (lorlatinib) is FDA approved for use in patients with ALK-positive non-small cell lung cancer (FDA.gov). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Lorlatinib | Lorbrena | PF-06463922|Lorviqua | ALK Inhibitor 32 ROS1 Inhibitor 20 | Lorbrena (lorlatinib) is a small molecule inhibitor of Alk and Ros1 fusion proteins, which may result in suppression of Alk and Ros1-mediated signaling thereby inhibiting cell growth and causing tumor regression (PMID: 26144315). Lorbrena (lorlatinib) is FDA approved for use in patients with ALK-positive non-small cell lung cancer (FDA.gov). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| EML4 - ALK ALK F1174C ALK D1203N | Advanced Solid Tumor | decreased response | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK Q1188_L1190del | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in significant metabolic response and stable disease lasting 11 months in an EML4-ALK-positive lung adenocarcinoma patient harboring ALK Q1188_L1190del who had previously progressed on Xalkori (crizotinib) and Zykadia (ceritinib) treatment (PMID: 33887694). | 33887694 |
| EML4 - ALK ALK V1180L | lung small cell carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor shrinkage after 5 months, with decrease in the size of intracranial and pulmonary lesions, in a patient with transformed small cell lung cancer from lung adenocarcinoma harboring EML4-ALK and ALK V1180L (PMID: 37907052). | 37907052 |
| ALK wild-type | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) did not inhibit growth of ALK wild-type neuroblastoma cells in culture (PMID: 26554404). | 26554404 |
| EML4 - ALK ALK L1196M ALK L1256F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK L1256F | lung adenocarcinoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) did not inhibit Alk kinase activity or proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002). | 30662002 |
| ALK I1171N ALK Y1278S | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, a neuroblastoma patient harboring ALK Y1278S progressed on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK I1171N (PMID: 38787533; NCT04477681). | 38787533 |
| EML4 - ALK ALK I1171N | sarcoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20) and ALK I1171N (PMID: 39188081). | 39188081 |
| ALK G1202R ALK R1275Q BRAF V600E | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK R1275Q developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK G1202R and BRAF V600E via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |
| EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512). | 38448512 |
| EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Lorbrena (lorlatinib) treatment in culture (PMID: 31943796). | 31943796 |
| EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK F1174V | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a complete response with a progression-free survival of 12.3 months, overall survival of 28.1 months, and a duration of treatment of 13.8 months in a patient with lung adenocarcinoma harboring EML4-ALK (e2:e20) with ALK F1174V (PMID: 39500140). | 39500140 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response lasting 10 months in a pediatric patient with metastatic neuroblastoma harboring ALK F1174L, along with MYCN amplification (PMID: 39177282). | 39177282 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response in 3 of 5 patients and a partial response in 1 of 5 patients with neuroblastoma harboring ALK F1174L (PMID: 37561984). | 37561984 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). | 26554404 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, neuroblastoma cells harboring ALK F1174L were resistant to Lorbrena (lorlatinib) in culture (PMID: 30322862). | 30322862 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in partial remission in a neuroblastoma patient harboring ALK F1174L (PMID: 38787533; NCT04477681). | 38787533 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting 13 mo in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1174L and PIK3CA C692Ffs*8, who had previously progressed on combination therapy with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan (PMID: 34210658). | 34210658 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a minor response with stable disease in a neuroblastoma patient harboring ALK F1174L (PMID: 37147298; NCT03107988). | 37147298 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Preclinical | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment induced tumor regression in a transgenic mouse model of neuroblastoma harboring ALK F1174L (PMID: 27483357). | 27483357 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease after 4 cycles in a pediatric patient with neuroblastoma harboring ALK F1174L (PMID: 36765519). | 36765519 |
| ALK F1174L | neuroblastoma | predicted - sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited downstream signaling, viability, and invasion in neuroblastoma cell lines harboring ALK F1174L in culture, and decreased tumor growth and increased survival in cell line xenograft models (PMID: 38032104). | 38032104 |
| ALK rearrange ALK L1196M ALK G1202R | lung non-small cell carcinoma | resistant | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is not indicated for use as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M and G1202R compound mutations (NCCN.org). | detail... |
| ALK rearrange ALK L1196M ALK G1202R | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R and ALK L1196M developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK G1202K | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, fourth-line Lorbrena (lorlatinib) treatment resulted in symptom improvement and response in lung disease with a progression-free survival lasting 4 months in an EML4-ALK positive a patient with lung adenocarcinoma patient harboring EML4-ALK and an acquired ALK G1202K, who had previously progressed on Xalkori (crizotinib) and Alecensa (alectinib) treatment (PMID: 33790576). | 33790576 |
| ALK G1202R ALK R1275Q | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing G1202R was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). | 37147298 |
| EML4 - ALK ALK I1171N ALK D1203N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and ALK D1203N in culture (PMID: 39269178). | 39269178 |
| EML4 - ALK ALK I1171N ALK D1203N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| ALK rearrange ALK D1203N | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK D1203N was identified in 24% (7/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). | 31358542 |
| EML4 - ALK ALK D1203N | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK D1203N | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). | 33627640 |
| ALK F1245V | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a complete response of marrow disease in a neuroblastoma patient harboring ALK F1245V, along with NF1 P2472fs and BRCA2 F2410fs (PMID: 37147298; NCT03107988). | 37147298 |
| EML4 - ALK | epithelioid inflammatory myofibroblastic sarcoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a pathological complete response in a patient with epithelioid inflammatory myofibroblastic sarcoma harboring EML4-ALK (e6:e20) (PMID: 39144623). | 39144623 |
| ALK fusion | Erdheim-Chester disease | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). | detail... |
| EML4 - ALK ALK I1171S ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| ALK F1245C | neuroblastoma | sensitive | Lorlatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1245C in culture, and induced rapid and sustained complete tumor regression in patient-derived xenograft models harboring ALK F1245C (PMID: 26554404). | 26554404 |
| EML4 - ALK ALK S1206Y | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 26144315). | 26144315 |
| EML4 - ALK ALK S1206Y | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK S1206Y in culture (PMID: 31446141). | 31446141 |
| ALK fusion ALK L1196M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). | 35726063 |
| ALK fusion ALK G1202R ALK S1206F ALK G1269A | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK S1206F and ALK G1269A were identified as acquired mutations in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). | 35726063 |
| ALK fusion ALK G1202R | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response with a progression-free survival of 3.9 months, overall survival of 12.3 months, and a duration of treatment of 4.9 months in a patient with lung adenocarcinoma harboring an ALK fusion with ALK G1202R (PMID: 39500140). | 39500140 |
| EML4 - ALK ALK I1171T ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK F1174C | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). | 26698910 |
| ALK F1174L HRAS Q61L | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, HRAS Q61L was identified in a post-progression biopsy in a pediatric patient with metastatic neuroblastoma harboring ALK F1174L, who previously achieved a partial response on Lorbrena (lorlatinib) treatment (PMID: 39177282). | 39177282 |
| EML4 - ALK ALK I1171N | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK I1171N | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N demonstrated resistance to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK F1174L ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK F1174L and ALK G1202R compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). | 31585938 |
| EML4 - ALK ALK L1196M ALK G1202R ALK D1203N | large cell neuroendocrine carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M, ALK D1203N, and ALK G1202R were identified on post-progression biopsy in a patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20), who previously achieved disease stabilization for 8 months with Lorbrena (lorlatinib) treatment (PMID: 36207130). | 36207130 |
| EML4 - ALK ALK C1156Y ALK F1174V | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK | osteosarcoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease for nearly 60 weeks in a patient with metastatic osteosarcoma harboring EML4-ALK, who previously progressed on Alecensa (alectinib) treatment (PMID: 38096470). | 38096470 |
| EML4 - ALK ALK L1152R | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 26144315). | 26144315 |
| EML4 - ALK ALK L1152R | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK L1152R in culture (PMID: 31446141). | 31446141 |
| ALK rearrange ALK I1171X | lung non-small cell carcinoma | predicted - sensitive | Lorlatinib | Clinical Study | Actionable | In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring I1171X (n=8), with an objective response rate of 75% (6/8; 95% CI 35.0-97.0), a median duration of response of 4.2 months (95% CI 2.8-4.2), and a median progression-free survival of 5.5 months (95% CI 4.1-6.9) (PMID: 30892989; NCT01970865). | 30892989 |
| ALK F1245C | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells overexpressing ALK F1245C in culture (PMID: 26554404). | 26554404 |
| ALK F1245C | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK F1245C in culture (PMID: 27483357). | 27483357 |
| EML4 - ALK ALK F1174C ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK C1156Y | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK C1156Y in culture (PMID: 31446141). | 31446141 |
| EML4 - ALK ALK C1156Y | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK C1156Y | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorlatinib (PF-06463922) inhibited growth and ALK phosphorylation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK L1196Q | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). | 33627640 |
| ALK amp | neuroblastoma | sensitive | Lorlatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a panel of ALK-amplified neuroblastoma cell lines in culture, and inhibited tumor growth in a patient-derived xenograft (PDX) model (PMID: 36602782). | 36602782 |
| ALK amp | neuroblastoma | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited growth of ALK-amplified neuroblastoma cells in culture (PMID: 26554404). | 26554404 |
| EML4 - ALK ALK C1156Y ALK D1203N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK D1203N was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| ALK F1174L NRAS Q61K | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of NRAS Q61K in a neuroblastoma cell line harboring ALK F1174L conferred resistance to Lorbrena (lorlatinib) in culture (PMID: 35689207). | 35689207 |
| EML4 - ALK ALK V1180L | lung non-small cell carcinoma | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis of non-small cell lung carcinoma cells harboring ALK V1180L in the context of EML4-ALK in culture (PMID: 26144315). | 26144315 |
| EML4 - ALK ALK V1180L ALK G1202R | large cell neuroendocrine carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical improvement and regression of lung lesions after 4 weeks of therapy in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations; however, new bone lesions and progression of the brain mass was seen, and significant progressive disease developed after 3 months (PMID: 34994612). | 34994612 |
| EML4 - ALK ALK I1171N ALK G1202R | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a lung adenocarcinoma patient harboring EML4-ALK with ALK I1171N and G1202R, along with ALK-ENC1 (PMID: 37007089). | 37007089 |
| ALK fusion | lung non-small cell carcinoma | sensitive | Lorlatinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (Study B7461006) that supported FDA approval, first-line Lorbrena (lorlatinib) treatment resulted in a significantly improved 12-mo progression-free survival rate (78% vs 39%, HR 0.28, p<0.0010) and a response rate of 76% (113/149) vs 58% (85/147) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer, and led to an intracranial response rate of 71% (12/14) vs 23% (3/13) in patients with measurable CNS metastases (PMID: 33207094; NCT03052608). | 33207094 detail... detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase I | Actionable | In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). | detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | Lorlatinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). | detail... 30413378 detail... |
| ALK fusion | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase III | Actionable | In a Phase III trial (CROWN), Lorbrena (lorlatinib) treatment (n=149) demonstrated superior efficacy compared to Xalkori (crizotinib) (n=147) at 5-year follow-up in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients, with improved median progression-free survival (PFS, not reached vs 9.1 months, HR 0.19), 5-year PFS rate (60% vs 8%), and median time to intracranial progression (not reached vs 16.4 months) (PMID: 38819031; NCT03052608). | 38819031 |
| EML4 - ALK ALK L1196P | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196P was identified in the post-progression circulating tumor DNA of a patient with relapsed non-small cell lung cancer harboring EML4-ALK treated with Lorbrena (lorlatinib), and in a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512). | 38448512 |
| EML4 - ALK ALK F1245V | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). | 33627640 |
| ALK F1245I | neuroblastoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, Lorbrena (lorlatinib) treatment resulted in a partial response in a pediatric patient with neuroblastoma harboring ALK F1245I, inhibited viability of patient-derived cells in culture, decreased tumor growth and prolonged event-free survival in a patient-derived xenograft model (PMID: 37523146; NCT03336931). | 37523146 |
| EML4 - ALK ALK C1156Y ALK F1174C | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| ALK rearrange ALK F1174L | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). | 31358542 |
| EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK culture and resulted in only 30% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK C1156Y ALK I1171T | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| ALK L1196M ALK R1275Q | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing L1196M was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). | 37147298 |
| EML4 - ALK ALK F1174L | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK F1174L in the context of EML4-ALK in culture (PMID: 26144315). | 26144315 |
| EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| ALK F1174I | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK F1174I in culture (PMID: 27483357). | 27483357 |
| ALK F1174V | neuroblastoma | sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited proliferation of a neuroblastoma cell line harboring ALK F1174V in culture and inhibited tumor growth in a cell line xenograft model (PMID: 27483357). | 27483357 |
| ALK F1174V | neuroblastoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting greater than 20 months in a patient with neuroblastoma harboring ALK F1174V (PMID: 37561984). | 37561984 |
| ROS1 D2033N | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 D2033N in culture (PMID: 32918045). | 32918045 |
| EML4 - ALK ALK F1174L ALK E1210K ALK G1269A | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209). | 35123209 |
| ALK rearrange ALK F1174X | lung non-small cell carcinoma | predicted - sensitive | Lorlatinib | Clinical Study | Actionable | In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK F1174X (n=12), with an objective response rate of 42% (5/12; 95% CI 15.0-72.0), a median duration of response not reached (NR), and a median progression-free survival of 7.4 months (95% CI 2.8-NR) (PMID: 30892989; NCT01970865). | 30892989 |
| ALK F1174L PIK3CA H1047R | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired PIK3CA H1047R via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |
| ALK G1269A | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK G1269A in culture (PMID: 27483357). | 27483357 |
| EML4 - ALK ALK C1156Y | lung non-small cell carcinoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation ALK C1156Y, was treated with Lorlatinib (PF-06463922) and displayed a 41% reduction in tumor growth after 5 weeks of treatment (PMID: 26698910; NCT01970865). | 26698910 |
| EML4 - ALK ALK C1156Y ALK I1171N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and C1156Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| ALK D1091N | neuroblastoma | predicted - sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) decreased viability of a neuroblastoma cell line harboring ALK D1091N in culture (PMID: 38032104). | 38032104 |
| ROS1 L2026M | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 L2026M in culture (PMID: 32918045). | 32918045 |
| EML4 - ALK ALK I1171T ALK F1174L ALK L1196M ALK D1203N ALK E1210K ALK G1269A | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M, D1203N, and I1171T were identified at the time of progression on Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK G1269A, ALK F1174L, and ALK E1210K (PMID: 35123209). | 35123209 |
| ALK rearrange ALK L1196M | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK L1196M (NCCN.org). | detail... |
| ALK rearrange ALK L1196M | lung non-small cell carcinoma | sensitive | Lorlatinib | Clinical Study | Actionable | In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK L1196M (n=12), with an objective response rate of 67% (8/12; 95% CI 35.0-90.0), a median duration of response not reached (NR) (95% CI 5.2-NR), and a median progression-free survival not reached (95% CI 2.8-NR) (PMID: 30892989; NCT01970865). | 30892989 |
| ALK rearrange ALK I1171N ALK D1203N | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| EML4 - ALK | lung non-small cell carcinoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase III trial (CROWN), Lorbrena (lorlatinib) therapy resulted in an objective response rate (ORR) of 81% (120/149, 15 complete and 105 partial responses) and a median progression-free survival (mPFS) that was not reached at 5-year follow-up in ALK-positive non-small cell lung cancer patients, with an ORR of 80%, 100%, and 83% and an mPFS of 64.3 mo, not reached, and 60.0 mo in patients with EML4-ALK variants 1 (n=20), 2 (n=7), and 3a/b (n=18), respectively (PMID: 38819031; NCT03052608). | 38819031 |
| EML4 - ALK | lung non-small cell carcinoma | sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells harboring EML4-ALK fusion, and reduced intracranial tumor size in cell line xenograft models (PMID: 26144315). | 26144315 |
| ALK rearrange ALK G1202R ALK L1204V ALK G1269A | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, ALK G1269A and L1204V were identified as acquired mutations in an ALK-positive non-small cell lung cancer patient harboring ALK G1202R who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK I1171N | lung non-small cell carcinoma | sensitive | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited cell viability, decreased downstream ALK signaling, and induced apoptosis in patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture (PMID: 33627640). | 33627640 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase I | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 50% (6/12) of patients with non-small cell lung carcinoma harboring a ROS1 rearrangement (PMID: 29074098; NCT03052608). | 29074098 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring a ROS1 rearrangement, or as a next-line therapy in patients with ROS1-rearranged non-small cell lung cancer who have not received prior ROS1 inhibitor therapy (PMID: 30285222, Version Update 15 Sept 2020; ESMO.org). | 30285222 detail... |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase Ib/II | Actionable | In a Phase I/II trial, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 62% (13/21) in tyrosine kinase inhibitor (TKI)-naive and 35% (14/40) in previous Xalkori (crizotinib)-treated patients with non-small cell lung cancer harboring ROS1 rearrangements, intracranial responses were observed in 64% (7/11) of TKI-naive patients and 50% (12/24) of previous Xalkori (crizotinib)-treated patients (PMID: 31669155; NCT01970865). | 31669155 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as subsequent therapy in patients with advanced or metastatic ROS1-rearranged non-small lung cancer (NCCN.org). | detail... |
| EML4 - ALK ALK L1196M ALK G1202R | lung non-small cell carcinoma | resistant | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK L1196M was resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 39269178). | 39269178 |
| EML4 - ALK ALK I1171N ALK F1174I | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, Lorbrena (lorlatinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK F1174C ALK L1196M | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C, who previously responded to Lorbrena (lorlatinib) treatment (PMID: 36093526). | 36093526 |
| EML4 - ALK ALK D1203N ALK E1210K | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK I1171T | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK I1171T | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1174V in culture (PMID: 31446141). | 31446141 |
| ALK Y1278S | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK Y1278S in culture (PMID: 27483357). | 27483357 |
| ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as first-line therapy for patients with advanced, recurrent, metastatic, or inoperable inflammatory myofibroblastic tumor harboring ALK translocations (NCCN.org). | detail... |
| ALK rearrange ALK G1202R ALK G1269A | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK G1202R ALK G1269A developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| ALK rearrange ALK L1196M ALK D1203N | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with lung adenocarcinoma harboring ALK rearrangement and acquired ALK L1196M, ALK D1203N mutations demonstrated primary resistance to Lorbrena (lorlatinib) treatment, resulted in immediate disease progression (PMID: 31585938). | 31585938 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase I | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608). | 29074098 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as subsequent therapy for patients who have progressed on second-generation ALK inhibitors (PMID: 30596843; ESMO.org). | 30596843 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). | detail... detail... 30413378 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as preferred first-line therapy and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase III | Actionable | In a Phase III trial (CROWN), Lorbrena (lorlatinib) treatment (n=149) demonstrated superior efficacy compared to Xalkori (crizotinib) (n=147) at 5-year follow-up in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients, with improved median progression-free survival (PFS, not reached vs 9.1 months, HR 0.19), 5-year PFS rate (60% vs 8%), and median time to intracranial progression (not reached vs 16.4 months) (PMID: 38819031; NCT03052608). | 38819031 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase II | Actionable | In a Phase II trial, Lorbrena (lorlatinib) treatment resulted in an intracranial disease control rate of 95% (21/22), intracranial objective response rate of 59% (13/22; 6 complete responses, 7 partial responses), a median intracranial progression-free survival (PFS) rate of 24.6 months, and a 12-month PFS rate of 79% in patients with ALK-rearranged non-small cell lung cancer, who previously demonstrated central nervous system progression on second-generation ALK inhibitors (PMID: 35584349; NCT02927340). | 35584349 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase Ib/II | Actionable | In a Phase I/II trial, Lorbrena (lorlatinib) treatment resulted in an objective response rate (ORR) of 82.4% (14/17, all partial responses (PR)) and 63.6% (21/33, all PR) in Asian and non-Asian patients with ALK-positive non-small cell lung cancer who had prior Xalkori (crizotinib) treatment and an ORR of 47.2% (25/53, 2 complete responses, 23 PR) and 30.1% (22/73, all PR) in patients previously treated with any second-generation ALK inhibitor (PMID: 35660971; NCT01970865). | 35660971 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (Study B7461006) that supported FDA approval, first-line Lorbrena (lorlatinib) treatment resulted in a significantly improved 12-mo progression-free survival rate (78% vs 39%, HR 0.28, p<0.0010) and a response rate of 76% (113/149) vs 58% (85/147) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer, and led to an intracranial response rate of 71% (12/14) vs 23% (3/13) in patients with measurable CNS metastases (PMID: 33207094; NCT03052608). | 33207094 detail... detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement who have progressed on an ALK tyrosine kinase inhibitor (PMID: 30285222; ESMO.org). | 30285222 detail... |
| EML4 - ALK ALK C1156Y ALK F1174I | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174I was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK in culture and resulted in only 18% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1202R in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512). | 38448512 |
| EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and L1196M were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and C1156Y were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534). | 29650534 |
| ALK R1275Q | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells overexpressing ALK R1275Q in culture (PMID: 26554404). | 26554404 |
| EML4 - ALK ALK T1151M ALK G1202R | lung non-small cell carcinoma | resistant | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK, ALK G1202R, and ALK T1151M was resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 39269178). | 39269178 |
| EML4 - ALK ALK R1181H | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited proliferation of cells expressing EML4-ALK and ALK R1181H in culture (PMID: 38960389). | 38960389 |
| EML4 - ALK | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 26698910). | 26698910 |
| ALK rearrange ALK I1171N ALK L1198F | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung cancer patient harboring ALK I1171N and L1198F in cis in the context of EML4-ALK demonstrated primary resistance to Lorlatinib (PF-06463922) (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK E1210K | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK E1210K in culture (PMID: 31446141). | 31446141 |
| EML4 - ALK ALK E1210K | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). | 27432227 |
| ALK rearrange ALK T1151M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). | 31439588 |
| ALK F1174L | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK F1174L in culture (PMID: 27483357). | 27483357 |
| ALK F1174L | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells overexpressing ALK F1174L in culture (PMID: 26554404). | 26554404 |
| ALK fusion ALK T1151dup | lung non-small cell carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in shrinkage of the pulmonary and uterine lesions in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins), and the patient remained recurrence-free over 1 year of treatment (PMID: 34184417). | 34184417 |
| EML4 - ALK ALK I1171T | lung non-small cell carcinoma | sensitive | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315). | 26144315 |
| EML4 - ALK ALK V1180L | lung cancer | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response lasting 20 months in a patient with lung cancer harboring EML4-ALK with ALK V1180L (PMID: 39363320; NCT02517892). | 39363320 |
| ALK R1192P | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK R1192P in culture (PMID: 27483357). | 27483357 |
| EML4 - ALK ALK T1151K | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK | lung mucoepidermoid carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic pulmonary mucoepidermoid carcinoma harboring EML4-ALK (e6:e20) (PMID: 39259069). | 39259069 |
| EML4 - ALK | lung mucoepidermoid carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with pulmonary mucoepidermoid carcinoma harboring EML4-ALK (e20:e20) (PMID: 39267825). | 39267825 |
| EML4 - ALK ALK L1196M | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 27432227). | 27432227 |
| EML4 - ALK ALK L1196M | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK L1196M | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK C1156Y ALK L1196M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung cancer patient with EML4-ALK, ALK G1202R, ALK L1196M, and ALK V1180L prior to Lorbrena (lorlatinib) treatment demonstrated loss of the V1180L variant and acquisition of ALK C1156Y following progression on Lorbrena (lorlatinib) (PMID: 31358542). | 31358542 |
| ROS1 fusion | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase I | Actionable | In a Phase I clinical trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). | detail... |
| ALK I1170N | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in complete remission in a neuroblastoma patient harboring ALK I1170N (PMID: 38787533; NCT04477681). | 38787533 |
| EML4 - ALK ALK C1156Y ALK I1171T ALK L1198F | lung non-small cell carcinoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a patient-derived non-small cell lung cancer cell line harboring EML4-ALK (e6:e19) with ALK C1156Y, I1171T, and L1198F was resistant to Lorbrena (lorlatinib) in culture (PMID: 37748191). | 37748191 |
| EML4 - ALK ALK I1171N ALK L1196M ALK G1202R | malignant pleural mesothelioma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK with ALK L1196M and ALK I1171N who previously responded to Lorbrena (lorlatinib) treatment (PMID: 32600123). | 32600123 |
| EML4 - ALK ALK L1196M ALK D1203N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and ALK D1203N compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). | 31585938 |
| EML4 - ALK ALK L1196M ALK D1203N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK I1171N ALK L1196M | malignant pleural mesothelioma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor regression and a partial response lasting 3.6 months in a patient with malignant pleural mesothelioma harboring EML4-ALK, ALK L1196M, and ALK I1171N (PMID: 32600123). | 32600123 |
| ALK fusion | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in reduction of the brain metastases in a patient with ALK-positive lung adenocarcinoma who had been previously treated with Alecensa (alectinib) and Xalkori (crizotinib) (PMID: 35373538). | 35373538 |
| ALK fusion ALK G1202R ALK L1204V ALK G1269A | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1204V and ALK G1269A were identified as acquired mutations in a non-small cell lung cancer patient harboring an ALK fusion with ALK G1202R who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141). | 31446141 |
| EML4 - ALK ALK L1198F ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
| ALK fusion ALK G1202R | lung non-small cell carcinoma | sensitive | Lorlatinib | Phase I | Actionable | In a Phase I trial, treatment with Lorlatinib (PF-06463922) demonstrated safety and resulted in durable responses in patients with ALK-positive non-small cell lung cancer, including patients harboring ALK G1202R (J Clin Oncol 34, 2016 (suppl; abstr 9009)). | detail... |
| ALK F1174L ALK G1202R | neuroblastoma | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a neuroblastoma cell line harboring ALK F1174L and expressing G1202R was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). | 37147298 |
| ALK act mut | neuroblastoma | sensitive | Lorlatinib | Phase I | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment was well tolerated and resulted in a modified response rate of 30% (7/23) in children and 67% (10/15) in adults with neuroblastoma harboring an ALK activating mutation, including ALK F1174C, F1174L, R1275Q, or R1275L, F1245Y, F1245L, D1276_R1279delinsE, or amplification (PMID: 37012551; NCT03107988). | 37012551 |
| EML4 - ALK ALK D1203N ALK F1245V | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK | neuroblastoma | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells harboring EML4-ALK in culture (PMID: 26554404). | 26554404 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited tumor growth of a cell line xenograft model expressing EML4-ALK with ALK G1202R (PMID: 35820889). | 35820889 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited tumor growth in a mouse cell line xenograft model expressing EML4-ALK and ALK G1202R (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202R demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). | 27432227 |
| ROS1 G2032R | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 G2032R in culture (PMID: 32918045). | 32918045 |
| EML4 - ALK ALK F1174I ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK I1171N | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in all lesions including lesions within the CNS with a progression-free survival of 14 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and ALK I1171N (PMID: 38623748). | 38623748 |
| EML4 - ALK ALK E1129V ALK I1171N | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and E1129V were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| ALK del exon4-11 | neuroblastoma | sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited proliferation of a neuroblastoma cell line harboring deletion of ALK exons 4-11 in culture and inhibited tumor growth in a cell line xenograft model (PMID: 27483357). | 27483357 |
| ROS1 fusion ROS1 S1986F ROS1 L2000V | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-small cell lung cancer harboring a ROS1 fusion who had progressed on Xalkori (crizotinib) was subsequently treated with Lorbrena (lorlatinib) but progression ensued and post treatment biopsy revealed acquisition of ROS1 S1986F and ROS1 L2000V (PMID: 33685866). | 33685866 |
| EML4 - ALK ALK F1174C ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| ALK R1275Q | neuroblastoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in 3 complete responses and 1 partial response in 4 pediatric patients with relapsed or refractory neuroblastoma harboring ALK R1275Q, with treatment ongoing for an average of 52 months (PMID: 39177282). | 39177282 |
| ALK R1275Q | neuroblastoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a complete response in a neuroblastoma patient harboring a germline ALK R1275Q, who was on treatment for 18 months and remained in remission at 5 years (PMID: 37147298; NCT03107988). | 37147298 |
| ALK R1275Q | neuroblastoma | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) decreased viability of neuroblastoma cell lines harboring ALK R1275Q in culture (PMID: 38032104). | 38032104 |
| ALK R1275Q | neuroblastoma | sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, resulted in growth inhibition of neuroblastoma cells over expressing ALK R1275Q in culture and induced rapid and sustained complete tumor regression in cell line xenograft models (PMID: 26554404). | 26554404 |
| ALK R1275Q | neuroblastoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in 3 of 4 patients with neuroblastoma harboring ALK R1275Q (PMID: 37561984). | 37561984 |
| EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK E1129V ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and E1129V were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK C1156Y ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK I1171N ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| ROS1 S1986Y | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 S1986Y in culture (PMID: 32918045). | 32918045 |
| ALK rearrange RB1 C706F TP53 loss | lung small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, RB1 C706F and loss of exons 1-11 in TP53 were identified in the pericardium infiltrating small cell lung cancer that developed while on Lorlatinib (PF-06463922) treatment in a patient with ALK-rearranged non-small cell lung carcinoma (PMID: 28285684). | 28285684 |
| EML4 - ALK ALK L1196M ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK G1202R | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response with a progression-free survival of 21.2 months, overall survival of 34.0 months, and a duration of treatment of 24.2 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) with ALK G1202R (PMID: 39500140). | 39500140 |
| EML4 - ALK ALK G1202R | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R (PMID: 35328235). | 35328235 |
| EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK G1202R | lung cancer | conflicting | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK ALK G1202R | lung cancer | conflicting | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis in transformed cells over expressing ALK G1202R in the context of EML4-ALK in culture and in cell line xenograft models (PMID: 26144315). | 26144315 |
| ALK fusion ALK D1203N ALK E1210K ALK G1269A | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1269A was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK D1203N and ALK E1210K who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). | 35726063 |
| EML4 - ALK ALK L1196M ALK D1203N | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e19:e20) and ALK D1203N who responded to Lorbrena (lorlatinib) treatment was found to have acquired ALK L1196M upon disease progression (PMID: 38149055). | 38149055 |
| ALK rearrange ALK F1174C | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK F1174C/L was identified in 14% (4/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). | 31358542 |
| ALK fusion ALK C1156Y ALK L1198F | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1198F was identified as an acquired mutation in a non-small cell lung cancer patient harboring an ALK fusion with ALK C1156Y who developed resistance to Lorbrena (lorlatinib) after initial response (PMID: 35726063). | 35726063 |
| ALK I1171T ALK R1192P ALK L1196M ALK F1245V | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK F1245V developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired additional ALK variants, I1171T, R1192P, and L1196M, via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |
| EML4 - ALK ALK G1202R | sarcoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20) and ALK I1171N experienced progressive disease on treatment with Lorbrena (lorlatinib) and was found to have lost ALK I1171N and acquired ALK G1202R (PMID: 39188081). | 39188081 |
| EML4 - ALK ALK C1156Y ALK G1269A | lung adenocarcinoma | unknown | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 6.9 months of therapy in a patient with lung adenocarcinoma harboring EML4-ALK, ALK C1156Y and ALK G1269A were identified in biopsies at disease progression, however, cells derived from the patient-derived xenograft (PDX) model of the patient and transformed cells expressing the compound mutation demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 31585938). | 31585938 |
| ALK F1174L FGFR1 N546K | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired FGFR1 N546K via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |
| EML4 - ALK ALK G1202R ALK S1206F ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| ALK rearrange ALK F1174L ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). | 31439588 |
| EML4 - ALK ALK G1269A | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1269A | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910). | 26698910 |
| ALK F1174L ALK G1202R ALK D1203N ALK amp | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK amplification, and ALK G1202R and D1203N each in cis with F1174L via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |
| EML4 - ALK ALK G1123S | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141). | 31446141 |
| EML4 - ALK ALK G1202R | lung squamous cell carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, third-line Lorbrena (lorlatinib) treatment resulted in a progression-free survival of 7 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK and ALK G1202R (PMID: 34376997). | 34376997 |
| EML4 - ALK ALK F1245C | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1245C in culture (PMID: 31446141). | 31446141 |
| EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). | 34158340 |
| ALK rearrange ALK F1174C ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). | 31439588 |
| ALK G1202R ALK D1276_R1279delinsE | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a complete metabolic response and a partial anatomic response in a neuroblastoma patient harboring ALK D1276_R1279delinsE and G1202R, who remained on the treatment for over 27 cycles (PMID: 37147298; NCT03107988). | 37147298 |
| ROS1 D2113N | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture and inhibited tumor growth and increased survival in a cell line xenograft model (PMID: 37587872). | 37587872 |
| EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK G1202R ALK S1206F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). | 35726063 |
| ALK F1245Y HRAS G13R | neuroblastoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a neuroblastoma patient harboring ALK F1245Y developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired HRAS G13R via circulating tumor DNA (PMID: 37147298; NCT03107988). | 37147298 |
| EML4 - ALK ALK L1256F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK | lung adenocarcinoma | sensitive | Lorlatinib | Preclinical - Pdx | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment decreased tumor growth in a patient-derived xenograft (PDX) model of lung adenocarcinoma harboring EML4-ALK (PMID: 34911818). | 34911818 |
| EML4 - ALK | lung adenocarcinoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a progression-free survival of 1.9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20) and inhibited growth of a patient-derived organoid cell line in culture (PMID: 38983150). | 38983150 |
| EML4 - ALK | lung adenocarcinoma | sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in an intracranial response, with improvement of the metastatic brain lesions, in a patient with lung adenocarcinoma harboring EML4-ALK (e20:e20), who previously progressed on Alunbrig (brigatinib) (PMID: 38924375). | 38924375 |
| EML4 - ALK ALK I1171N ALK F1174L | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). | 33627640 |
| ALK F1174L ALK L1196M | neuroblastoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, two neuroblastoma patients harboring ALK F1174L developed progressive disease on treatment with Lorbrena (lorlatinib) and were found to have acquired ALK L1196M via circulating tumor DNA, and a neuroblastoma cell line harboring ALK F1174L and expressing L1196M was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298; NCT03107988). | 37147298 |
| EML4 - ALK ALK F1174C | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease lasting 6 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20) and ALK F1174C, who previously progressed on Xalkori (crizotinib) and Alunbrig (brigatinib) (PMID: 36093526). | 36093526 |
| EML4 - ALK ALK L1198F | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK L1198F | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F had reduced sensitivity to growth inhibition mediated by Lorbrena (lorlatinib) in comparison to wild-type EML4-ALK in culture (PMID: 26698910). | 26698910 |
| EML4 - ALK | colorectal carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical benefit and a progression-free survival of 11.5 months in a patient with metastatic colorectal carcinoma harboring EML4-ALK, whose disease progressed on initial Xalkori (crizotinib) treatment and did not respond to subsequent Alecensa (alectinib) treatment (PMID: 34036227). | 34036227 |
| ALK rearrange ALK G1269A | lung non-small cell carcinoma | predicted - sensitive | Lorlatinib | Clinical Study | Actionable | In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1269A (n=9), with an objective response rate of 89% (8/9; 95% CI 52.0-100.0), a median duration of response not reached (NR) (95% CI 5.6-NR), and a median progression-free survival not reached (95% CI 8.2-NR) (PMID: 30892989; NCT01970865). | 30892989 |
| EML4 - ALK ALK T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 3.7 months therapy in a patient with lung adenocarcinoma harboring EML4-ALK and ALK G1202R, at disease progression, ALK F1174L in cis wth ALK G1202R was identified in biopsies, and ALK C1156Y, G1269A, S1206F, and T1151M were identified in ctDNA (PMID: 31585938). | 31585938 |
| ROS1 S1986F | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 S1986F in culture (PMID: 32918045). | 32918045 |
| EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| ALK I1171N ALK pos | diffuse large B-cell lymphoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in an ongoing complete metabolic response 20 months post-transplant in a patient with an ALK-positive large B-cell lymphoma harboring ALK I1171N (PMID: 36809056). | 36809056 |
| ALK rearrange ALK G1202del | lung non-small cell carcinoma | predicted - sensitive | Lorlatinib | Clinical Study | Actionable | In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1202R or ALK G1202del (n=28), with an objective response rate of 57% (16/28; 95% CI 37.0-76.0), a median duration of response of 7 months (95% CI 6.1-24.4), and a median progression-free survival of 8.2 months (95% CI 5.6-25.6) (PMID: 30892989; NCT01970865). | 30892989 |
| ALK F1245Y | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response in a patient with neuroblastoma harboring ALK F1245Y (PMID: 37147298). | 37147298 |
| ALK F1174C | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a partial response in a neuroblastoma patient harboring ALK F1174C, along with CDKN2A A102V (PMID: 37147298; NCT03107988). | 37147298 |
| EML4 - ALK ALK C1156Y ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK I1171N | inflammatory myofibroblastic tumor | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in near resolution of the pleural effusion and decrease in pleural mass in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK and ALK I1171N (PMID: 37255276). | 37255276 |
| EML4 - ALK ALK T1151K ALK G1202R ALK S1206F | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK S1206F and ALK T1151K were identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R after the disease progressed on Lorbrena (lorlatinib) treatment (PMID: 35328235). | 35328235 |
| EML4 - ALK ALK C1156Y ALK L1198F | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a Phase I trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910; NCT01970865). | 26698910 |
| ALK rearrange ALK D1203N ALK E1210K ALK G1269A | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, ALK G1269A was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK E1210K and D1203N, who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK I1179V ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| ROS1 D2113G | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited proliferation of transformed cells expressing ROS1 D2113G in culture (PMID: 37587872). | 37587872 |
| EML4 - ALK ALK F1174I | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK F1174C ALK G1202R | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174C were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). | 36201110 |
| EML4 - ALK ALK F1174V ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK G1202L | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with Lorbrena (lorlatinib) resulted in stable disease with a progression-free survival of 9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK G1202L, which was acquired after prior ALK inhibitor therapy (PMID: 33380260). | 33380260 |
| EML4 - ALK ALK F1174L ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK D1203N | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response and progression-free survival of 19 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e19:e20) and ALK D1203N (PMID: 38149055). | 38149055 |
| EML4 - ALK ALK L1196M | lung non-small cell carcinoma | sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells over expressing ALK L1196M in the context of EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26144315). | 26144315 |
| EML4 - ALK ALK C1156Y ALK L1256F | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
| EML4 - ALK ALK G1269A | lung non-small cell carcinoma | sensitive | Lorlatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and growth of non-small cell lung cancer (NSCLC) cells over expressing ALK G1269A in the context of EML4-ALK in culture and in cell line xenograft models, as well as inhibited growth of patient derived NSCLC cells harboring EML4-ALK ALK G1269A in culture (PMID: 26144315). | 26144315 |
| ALK rearrange ALK C1156Y ALK L1198F | lung non-small cell carcinoma | resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y ALK L1198F developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| ALK rearrange ALK C1156Y | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK C1156Y was identified in biopsies at disease progression after 16 months of Lorbrena (lorlatinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement, cells derived from patient's tumor were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). | 31585938 |
| EML4 - ALK ALK L1198R | Advanced Solid Tumor | predicted - resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Lorbrena (lorlatinib) in culture (PMID: 38448512). | 38448512 |
| EML4 - ALK ALK I1171S | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). | 33627640 |
| EML4 - ALK ALK I1171S | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). | 27432227 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | sensitive | Lorlatinib | Clinical Study | Actionable | In a clinical study, treatment with Lorbrena (lorlatinib) resulted in antitumor activity in ALK-rearranged non-small cell lung cancer patients harboring ALK G1202R or ALK G1202del (n=28), with an objective response rate of 57% (16/28; 95% CI 37.0-76.0), a median duration of response of 7 months (95% CI 6.1-24.4), and a median progression-free survival of 8.2 months (95% CI 5.6-25.6) (PMID: 30892989; NCT01970865). | 30892989 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer harboring ALK G1202R (NCCN.org). | detail... |
| EML4 - ALK ALK F1174C ALK E1210K | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, ALK F1174C, and ALK E1210K (PMID: 34378333). | 34378333 |
| EML4 - ALK ALK G1202del | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1202del in culture (PMID: 31446141). | 31446141 |
| EML4 - ALK ALK G1202del | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). | 27432227 |
| ALK Y1278S | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response in a neuroblastoma patient harboring ALK Y1278S (PMID: 38787533; NCT04477681). | 38787533 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT06333899 | Phase I | Lorlatinib Cisplatin + Cyclophosphamide + Lorlatinib + Vincristine Sulfate Carboplatin + Cyclophosphamide + Etoposide + Lorlatinib + Methotrexate + Vincristine Sulfate | Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion | Not yet recruiting | USA | NLD | DEU | CAN | AUS | 0 |
| NCT03052608 | Phase III | Lorlatinib Crizotinib | A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC | Active, not recruiting | USA | TUR | POL | NLD | ITA | GBR | FRA | ESP | DEU | CZE | CAN | BEL | AUS | ARG | 9 |
| NCT03126916 | Phase III | Doxorubicin 131I-MIBG Sargramostim Etoposide Melphalan Busulfan Isotretinoin Vincristine Sulfate Cisplatin Cyclophosphamide Thiotepa Dexrazoxane Lorlatinib Carboplatin Aldesleukin Topotecan Dinutuximab | Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL) | Active, not recruiting | USA | CAN | 1 |
| NCT04362072 | FDA approved | Lorlatinib | Study of Lorlatinib In People With ALK-positive Non-small Cell Lung Cancer | Completed | USA | POL | ITA | GBR | ESP | CHE | 1 |
| NCT02927340 | Phase II | Lorlatinib | A Study of Lorlatinib in Advanced ALK and ROS1 Rearranged Lung Cancer With CNS Metastasis in the Absence of Measurable Extracranial Lesions | Unknown status | USA | 0 |
| NCT04621188 | Phase II | Lorlatinib | Lorlatinib After Failure of First-line TKI in Patients With Advanced ROS1-positive NSCLC (ALBATROS) | Recruiting | FRA | 0 |
| NCT03737994 | Phase II | Cisplatin + Lorlatinib Carboplatin + Lorlatinib Ceritinib Alectinib + Cisplatin Alectinib + Carboplatin Ceritinib + Cisplatin Pemetrexed Disodium Carboplatin + Ceritinib Cisplatin + Ensartinib Carboplatin + Ensartinib Brigatinib + Cisplatin Brigatinib Alectinib Brigatinib + Carboplatin Ensartinib Cisplatin + Pemetrexed Disodium Crizotinib Carboplatin + Pemetrexed Disodium Lorlatinib | Targeted Treatment for ALK Positive Patients Who Have Previously Been Treated for Non-squamous Non-small Cell Lung Cancer | Active, not recruiting | USA | 0 |
| NCT04127110 | Phase II | Lorlatinib | Activity of Lorlatinib Based on ALK Resistance Mutations Detected on Blood in ALK Positive NSCLC Patients (ALKALINE) | Active, not recruiting | NOR | NLD | GBR | FRA | ESP | BEL | 1 |
| NCT03505554 | Phase II | Lorlatinib | A Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma (CRU3) | Recruiting | ITA | 0 |
| NCT05097599 | Phase II | Binimetinib + Encorafenib Trastuzumab deruxtecan Enfortumab vedotin-ejfv Talazoparib Lorlatinib | Strata PATH (Precision Indications for Approved Therapies) (Strata PATH) | Active, not recruiting | USA | 0 |
| NCT03107988 | Phase I | Cyclophosphamide + Lorlatinib + Topotecan Lorlatinib | NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922) | Active, not recruiting | USA | GBR | FRA | CAN | 0 |
| NCT03178071 | Expanded access | Lorlatinib | Expanded Access For Lorlatinib For Patients With Non Small Cell Lung Cancer Harboring Specific Molecular Alterations | No longer available | USA | 0 |
| NCT05144997 | FDA approved | Lorlatinib | Lorlatinib Continuation Study | Active, not recruiting | USA | FRA | ESP | 5 |
| NCT04111705 | Phase II | Lorlatinib | Lorlatinib After Failure of First-line Second-generation ALK Kinase Inhibitor in Patients With Advanced ALK-positive Non-small Cell Lung Cancer (ORAKLE) | Active, not recruiting | FRA | 0 |
| NCT02584634 | Phase I | Crizotinib Avelumab Lorlatinib | Study to Evaluate Safety, Efficacy, Pharmacokinetics And Pharmacodynamics Of Avelumab In Combination With Either Crizotinib Or PF-06463922 In Patients With NSCLC. (Javelin Lung 101) | Terminated | USA | ESP | AUS | 2 |
| NCT02925234 | Phase II | Crizotinib Sunitinib Niraparib Olaparib Lorlatinib Erdafitinib Talazoparib Dacomitinib Axitinib Panitumumab | The Drug Rediscovery Protocol (DRUP Trial) (DRUP) | Recruiting | NLD | 0 |
| NCT01970865 | Phase II | Lorlatinib Crizotinib | A Study Of PF-06463922 An ALK/ROS1 Inhibitor In Patients With Advanced Non Small Cell Lung Cancer With Specific Molecular Alterations | Completed | USA | ITA | FRA | ESP | DEU | CHE | CAN | BEL | AUS | 5 |
CKB BOOST