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Therapy Name | Brigatinib |
Synonyms | |
Therapy Description |
Alunbrig (brigatinib) is a multi-kinase inhibitor with selected activity against ALK, ROS1 fusions, FLT3, IGF1R and mutant EGFR, potentially resulting in decreased tumor growth (PMID: 27780853). Alunbrig (brigatinib) is FDA approved for use in patients with ALK-positive metastatic non-small cell lung cancer (FDA.gov). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Brigatinib | Alunbrig | AP26113 | ALK Inhibitor 33 EGFR Inhibitor (Pan) 64 FLT3 Inhibitor 69 IGF-1R Inhibitor 17 ROS1 Inhibitor 22 | Alunbrig (brigatinib) is a multi-kinase inhibitor with selected activity against ALK, ROS1 fusions, FLT3, IGF1R and mutant EGFR, potentially resulting in decreased tumor growth (PMID: 27780853). Alunbrig (brigatinib) is FDA approved for use in patients with ALK-positive metastatic non-small cell lung cancer (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK C1156Y | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK C1156Y | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK C1156Y | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). | 26698910 |
ALK rearrange ALK L1196M | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK L1196M was identified in 17% (12/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). | 31358542 |
ALK rearrange | Cancer of Unknown Primary | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines for patients with cancer of unknown primary harboring ALK rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org). | 30285222 detail... 36563965 |
EML4 - ALK ALK I1171S | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response with regression of the liver lesions and disease control in the intrathoracic and brain metastases lasting at least 9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e19) and ALK I1171S (PMID: 29981924). | 29981924 |
EML4 - ALK ALK I1171N ALK L1198H | Advanced Solid Tumor | predicted - resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171T ALK G1269A | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response lasting at least 7.4 months in a patient with advanced non-small cell lung cancer harboring EML4-ALK, ALK G1269A, and ALK I1171T who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936). | 36096442 |
ALK Y1278S | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK Y1278S was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
FLT3 exon 14 ins | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK I1171N ALK L1256F | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640). | 33627640 |
ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Brigatinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). | 30165392 |
EML4 - ALK ALK D1203N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK D1203N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). | 27432227 |
ALK R1192P | malignant pheochromocytoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response (PR) after 2 months of therapy and a sustained PR at 10 months in a patient with malignant pheochromocytoma harboring ALK R1192P (PMID: 34371380). | 34371380 |
EML4 - ALK ALK F1245C | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1245C in culture (PMID: 31446141). | 31446141 |
ROS1 rearrange | lung non-small cell carcinoma | no benefit | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) is not indicated for use in ROS1 rearranged non-small cell lung cancer patients whose disease became resistant to Xalkori (crizotinib) (NCCN.org). | detail... |
ROS1 rearrange | lung non-small cell carcinoma | no benefit | Brigatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Alunbrig (brigatinib) treatment resulted in a partial response in a patient with Xalkori (crizotinib)-naive non-small cell lung cancer (NSCLC) harboring ROS1 rearrangement, and resulted in 1 partial response and 1 stable disease in 7 patients with Xalkori (crizotinib)-resistant NSCLC harboring ROS1 rearrangements (PMID: 32462394). | 32462394 |
ALK F856S | hematologic cancer | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK F856S were sensitive to treatment with Alunbrig (brigatinib) in culture, demonstrating decreased cell viability (PMID: 26032424). | 26032424 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK F1174V in the context of EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269A, L1198F, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
ALK F1174V | neuroblastoma | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, neuroblastoma cells harboring ALK F1174V were sensitive to Alunbrig (brigatinib) in culture and in vivo, resulting in inhibition of both Alk activity and cell proliferation (PMID: 27049722). | 27049722 |
EML4 - ALK ALK V1180Y | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response, with a progression-free survival of 7.4 months, in a patient with advanced non-small cell lung cancer harboring EML4-ALK and ALK V1180Y who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936). | 36096442 |
EML4 - ALK | lung squamous cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a complete response in the lung and partial response in the brain lesions in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, with a progression-free survival of 11 months (PMID: 34376997). | 34376997 |
FLT3 exon 14 ins FLT3 F691I | Advanced Solid Tumor | decreased response | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing a FLT3-ITD mutation and FLT3 F691I demonstrated reduced sensitivity to Alunbrig (brigatinib) compared to cells expressing FLT3-ITD alone in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK A1200_G1201delinsW | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK who developed resistance to Alecensa (alectinib) following acquisition of ALK A1200_G1201delinsW demonstrated symptom improvement and stable disease for 4 months with Alunbrig (brigatinib) treatment (PMID: 34548910). | 34548910 |
EML4 - ALK ALK L1196Q | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174C ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | 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 Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1196M | large cell neuroendocrine carcinoma | no benefit | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a heavily pretreated patient with metastatic large cell neuroendocrine lung carcinoma harboring EML4-ALK (e20:e20) and ALK L1196M did respond to Alunbrig (brigatinib) treatment (PMID: 36207130). | 36207130 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1174C in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK F1174C | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK R1181H | lung adenocarcinoma | sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in an ongoing partial response after 12 months in a patient with lung adenocarcinoma harboring EML4-ALK and ALK R1181H, and in a preclinical study, inhibited proliferation of cells expressing EML4-ALK and ALK R1181H in culture (PMID: 38960389). | 38960389 |
ALK rearrange ALK I1171X | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK I1171X was identified in 24% (17/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). | 31358542 |
EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). | 25228534 |
EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK G1202R | lung adenocarcinoma | conflicting | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA, experienced disease progression after 2.5 months of Alunbrig (brigatinib) treatment, and only increased allelic frequency of ALK G1202R was detected at disease progression (PMID: 31585938). | 31585938 |
EML4 - ALK ALK G1202R | lung adenocarcinoma | conflicting | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response and 30 months of progression-free survival in a lung adenocarcinoma patient harboring EML4-ALK and de novo ALK G1202R (PMID: 35235872). | 35235872 |
EML4 - ALK ALK G1202R ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269A and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
ALK rearrange | anaplastic large cell lymphoma | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines as initial, second-line, and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). | detail... |
EML4 - ALK ALK E1210K | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK T1151M ALK G1202R | lung non-small cell carcinoma | resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response lasting 10 months in a patient with non-small cell lung cancer harboring EML4-ALK with ALK G1202R and ALK T1151M (PMID: 39363320; NCT02517892). | 39363320 |
EML4 - ALK ALK T1151M ALK G1202R | lung non-small cell carcinoma | resistant | Brigatinib | 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 Alunbrig (brigatinib) treatment in culture (PMID: 39269178). | 39269178 |
EML4 - ALK ALK I1171N ALK D1203N | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) did not inhibit viability of cells expressing EML4-ALK, ALK I1171N, and ALK D1203N in culture (PMID: 39269178). | 39269178 |
EML4 - ALK ALK S1206F | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206F in the context of EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK I1171T | Advanced Solid Tumor | predicted - sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK I1171T | Advanced Solid Tumor | predicted - sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing ALK I1171T in the context of EML4-ALK but to a lesser degree than cells expressing EML4-ALK in culture (PMID: 25228534). | 25228534 |
EML4 - ALK ALK I1171T | Advanced Solid Tumor | predicted - sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). | 33627640 |
FLT3 exon 14 ins FLT3 D835Y | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing a FLT3-ITD mutation and FLT3 D835Y in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK L1196P | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1196P were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK | large cell neuroendocrine carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a response in the primary tumor and brain metastases in a patient with large cell neuroendocrine carcinoma of the lung harboring EML4-ALK (e6:e20) (PMID: 39395329). | 39395329 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | 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 Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1196M ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1245V | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1152P | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152P in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK L1152P | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152P in the context of EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK L1198F ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK I1171N ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with L1198F in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK F1174C ALK D1203N | Advanced Solid Tumor | decreased response | Brigatinib | 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 Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). | 27432227 |
ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) 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 G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK G1269A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
ALK rearrange ALK V1180L | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical study, Alunbrig (brigatinib) treatment resulted in 1 partial response and 1 stable disease in a total of 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK V1180L (PMID: 29935304). | 29935304 |
EML4 - ALK ALK T1151dup | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK T1151dup in the context of EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK T1151dup | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578). | 35421578 |
ALK rearrange ALK D1203N | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK D1203N was identified at disease progression while on Alunbrig (brigatinib) treatment in a patient with ALK-positive non-small cell lung cancer (PMID: 29935304). | 29935304 |
EML4 - ALK ALK L1256F | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640). | 33627640 |
EML4 - ALK | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534). | 25228534 |
EML4 - ALK | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK S1206C ALK E1210K | lung non-small cell carcinoma | resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK E1210K eventually progressed on treatment with Alunbrig (brigatinib) and was subsequently found to have acquired another resistance mutation, ALK S1206C in cis (PMID: 29636358). | 29636358 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) 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 | Brigatinib | FDA approved - Has Companion Diagnostic | Actionable | In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501). | detail... detail... detail... |
ALK rearrange | lung non-small cell carcinoma | sensitive | Brigatinib | Clinical Study | Actionable | In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulting in an objective response rate of 17% (3/18) and stable disease in 50% (9/18) of patients with Alecensa (alectinib) refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304). | 29935304 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines as preferred first-line 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 | Brigatinib | FDA approved - Has Companion Diagnostic | Actionable | In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). | detail... 28475456 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222; ESMO.org). | detail... 30285222 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Brigatinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117). | 26438117 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Brigatinib | Phase Ib/II | Actionable | In a Phase I/II trial, Alunbrig (brigatinib) treatment resulted in an objective response rate of 100% (8/8) in ALK inhibitor-naive, ALK-rearranged non-small cell lung cancer (NSCLC) patients, 72% (51/71) in Xalkori (crizotinib) treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716; NCT01449461). | 27836716 |
ALK I1171N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK I1171N was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
EML4 - ALK ALK I1171N ALK L1196M | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640). | 33627640 |
ALK F1174L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK F1174L was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
EML4 - ALK ALK F1174L | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK F1174L | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were less sensitive to Alunbrig (brigatinib)-mediated growth inhibition compared to cells expressing EML4-ALK in culture (PMID: 27009859). | 27009859 |
ALK rearrange ALK I1171N | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical study, Alunbrig (brigatinib) treatment resulted in stable disease in 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171N (PMID: 29935304). | 29935304 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1198F and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | 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 Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
EML4 - ALK ALK L1198F ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174L ALK L1198V | lung non-small cell carcinoma | resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK progressed while being treated with Alunbrig (brigatinib) and was subsequently found to harbor two resistance mutations, ALK F1174L and ALK L1198V, which were both in cis (PMID: 29636358). | 29636358 |
EML4 - ALK ALK F1174I | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 17 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and ALK I1171N (PMID: 38623748). | 38623748 |
ALK R1192P | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK R1192P was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
EML4 - ALK ALK L1152R | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK L1152R | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK L1152R | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK G1123S | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK C1235R ALK C1237Y | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with relapsed non-small cell lung cancer harboring EML4-ALK developed progressive disease while on treatment with Alunbrig (brigatinib), and was found to have acquired ALK C1235R and ALK C1237Y in trans by liquid biopsy (PMID: 38448512). | 38448512 |
ALK R1275Q | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a transformed cell line expressing ALK R1275Q was sensitive to Alunbrig (brigatinib) in culture and in cell line xenograft models, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
ALK fusion | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a significant reduction of brain metastases in a patient with lung adenocarcinoma harboring an ALK fusion (PMID: 38158887). | 38158887 |
EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK L1196M and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK L1196M ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196M | lung non-small cell carcinoma | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of non-small cell lung cancer cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 21502504). | 21502504 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796). | 31943796 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK I1171S | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In preclinical studies, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859, PMID: 26698910). | 26698910 27009859 |
EML4 - ALK ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK G1202R ALK S1206F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). | 27780853 |
EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alunbrig (brigatinib) in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK G1202R | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK D1203N ALK E1210K | Advanced Solid Tumor | decreased response | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK G1202R | lung squamous cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, who previously responded to Alunbrig (brigatinib) treatment (PMID: 34376997). | 34376997 |
EML4 - ALK ALK C1237Y | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK C1237Y were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512). | 38448512 |
ALK positive | lung non-small cell carcinoma | no benefit | Brigatinib | Phase II | Actionable | In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy demonstrated limited efficacy in ALK-positive advanced non-small cell lung cancer patients who previously progressed on Alecensa (alectinib) or Zykadia (ceritinib) therapy, with an objective response rate (ORR) of 26.2% (27/103, 1 complete (CR) and 26 partial responses), duration of response of 6.3 mo, median progression-free survival of 3.8 mo, and intracranial ORR of 15% (8/55, 1 CR) in patients with CNS metastases (PMID: 36096442; NCT05421936). | 36096442 |
ALK rearrange ALK I1171T | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK I1171T (PMID: 29935304). | 29935304 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | conflicting | Brigatinib | 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 Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063). | 35726063 |
EML4 - ALK ALK C1156Y ALK L1198F | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F in the context of EML4-ALK were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). | 26698910 |
ALK V1180L | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (ALTA-2), Alunbrig (brigatinib) therapy resulted in a partial response, with a progression-free survival of 11 months, in a patient with advanced non-small cell lung cancer harboring ALK V1180L who previously progressed on Alecensa (alectinib) therapy (PMID: 36096442; NCT05421936). | 36096442 |
EML4 - ALK ALK L1196Q | lung non-small cell carcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and an acquired ALK L1196Q who progressed on prior Alecensa (alectinib) treatment, the response was ongoing after 17 months of treatment (PMID: 33209633). | 33209633 |
EML4 - ALK ALK F1174L ALK E1210K | lung adenocarcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK E1210K was identified at the time of progression on Alunbrig (brigatinib) treatment in a patient with lung adenocarcinoma who initially harbored EML4-ALK (e13:e20) and ALK G1269A, and also acquired ALK F1174L and lost ALK G1269A during Alunbrig (brigatinib) treatment (PMID: 35123209). | 35123209 |
ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in progressive disease in a patient with ALK-rearranged non-small cell lung cancer refractory to Alecensa (alectinib) treatment, ALK G1202R was identified in post-brigatinib biopsy (PMID: 29935304). | 29935304 |
ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK G1202R was identified in 33% (23/70) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received second-generation ALK TKI treatment, including Alecensa (alectinib) (n=46), Zykadia (ceritinib) (n=4), Alunbrig (brigatinib) (n=3), Ensartinib (X-396) (n=1), or more than 2 lines of TKIs (n=16) (PMID: 31358542). | 31358542 |
EML4 - ALK ALK L1198R | Advanced Solid Tumor | predicted - resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing EML4-ALK and ALK L1198R were moderately resistant to Alunbrig (brigatinib) in culture (PMID: 38448512). | 38448512 |
EML4 - ALK ALK R1192P | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK T1151K | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK G1269A | lung adenocarcinoma | sensitive | Brigatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of patient-derived organoids of lung adenocarcinoma harboring EML4-ALK and ALK G1269A in culture and resulted in tumor shrinkage in a patient-derived xenograft (PDX) model (PMID: 38360931). | 38360931 |
EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171S ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796). | 31943796 |
ALK A348D | hematologic cancer | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK A348D were sensitive to treatment with Alunbrig (brigatinib) in culture, demonstrating decreased cell viability (PMID: 26032424). | 26032424 |
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK G1269A, L1204V, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK | lung adenocarcinoma | sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a complete response with a reduction in the brain metastases in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 38158887). | 38158887 |
EML4 - ALK | lung adenocarcinoma | sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a progression-free survival of 3.2 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 | Brigatinib | Preclinical - Pdx | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment decreased tumor growth in a patient-derived xenograft (PDX) model of lung adenocarcinoma harboring EML4-ALK (PMID: 34911818). | 34911818 |
EML4 - ALK ALK I1171N ALK F1174I | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). | 27432227 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196M ALK D1203N | Advanced Solid Tumor | predicted - resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK FGFR1 amp | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Alunbrig (brigatinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, FGFR1 amplification (PMID: 29636358). | 29636358 |
ALK rearrange ALK T1151R | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in clinical improvement and a major response in tumor volume and metabolic activity in a patient with metastatic lung adenocarcinoma harboring an ALK rearrangement and ALK T1151R until disease progression 3 months later (PMID: 31027750). | 31027750 |
EML4 - ALK ALK G1202del | Advanced Solid Tumor | decreased response | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Alunbrig (brigatinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). | 27432227 |
ALK fusion | lung non-small cell carcinoma | sensitive | Brigatinib | Phase Ib/II | Actionable | In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716). | 24091716 |
ALK fusion | lung non-small cell carcinoma | sensitive | Brigatinib | FDA approved - Has Companion Diagnostic | Actionable | In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501). | detail... detail... detail... |
ALK fusion | lung non-small cell carcinoma | sensitive | Brigatinib | FDA approved - Has Companion Diagnostic | Actionable | In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). | 28475456 detail... |
EML4 - ALK | lung non-small cell carcinoma | sensitive | Brigatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited tumor growth in a non-small cell lung cancer cell line xenograft model harboring EML4-ALK (PMID: 37036582). | 37036582 |
EML4 - ALK | lung non-small cell carcinoma | sensitive | Brigatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited Alk phosphorylation and growth in non-small cell lung cancer cell lines harboring EML4-ALK in culture, and induced near complete tumor regression in cell line xenograft models (PMID: 27780853). | 27780853 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to Alunbrig (brigatinib) in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | 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 Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
EML4 - ALK ALK I1171N ALK L1198F | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196M | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK L1196M | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196M | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). | 27780853 |
EML4 - ALK ALK I1171N ALK F1174L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). | 33627640 |
ALK G1128A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK G1128A was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
EML4 - ALK ALK C1156Y ALK G1269A | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK in culture (PMID: 31585938). | 31585938 |
EML4 - ALK ALK D1203N ALK F1245V | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK L1196M ALK G1202R | lung non-small cell carcinoma | resistant | Brigatinib | 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 Alunbrig (brigatinib) treatment in culture (PMID: 39269178). | 39269178 |
EML4 - ALK ALK L1196M ALK G1202R | lung non-small cell carcinoma | resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M and ALK G1202R were identified in the post-progression circulating tumor DNA of a patient with non-small cell lung cancer harboring EML4-ALK who progressed on treatment with Alunbrig (brigatinib), and in a preclinical study, cells expressing EML4-ALK, ALK L1196M, and ALK G1202R were resistant to Alunbrig (brigatinib) in culture (PMID: 38448512, PMID: 36806896). | 36806896 38448512 |
EML4 - ALK ALK C1156Y ALK G1202R | Advanced Solid Tumor | resistant | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK C1156Y and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). | 34158340 |
ROS1 fusion | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ROS1 fusion proteins in culture (PMID: 27780853). | 27780853 |
ALK F1245C | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK F1245C was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
ALK fusion | Erdheim-Chester disease | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) 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 E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 10 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A (PMID: 36093526). | 36093526 |
EML4 - ALK ALK T1151M | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK V1180L ALK G1202R | large cell neuroendocrine carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations demonstrated further progressive disease 2 weeks after initiating Alunbrig (brigatinib) treatment (PMID: 34994612). | 34994612 |
ALK rearrange ALK V1180L ALK L1196M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1202R and ALK L1196M were identified at disease progression while on Alunbrig (brigatinib) treatment in liquid biopsy of a patient with ALK-positive non-small cell lung cancer also harboring an ALK V1180L (PMID: 29935304). | 29935304 |
FLT3 exon 14 ins FLT3 F691L | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing FLT3 ITD and F691L in culture (PMID: 27780853). | 27780853 |
ALK rearrange ALK L1196M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Brigatinib | Case Reports/Case Series | Actionable | In a Phase III trial (ALTA-1L), ALK L1196M and ALK G1202R were identified in the post-progression plasma ctDNA of a patient with ALK-positive non-small cell lung cancer who previously responded to treatment with Alunbrig (brigatinib) (PMID: 31668326). | 31668326 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT03868423 | Phase II | Brigatinib | Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers | Withdrawn | USA | 0 |
NCT03535740 | Phase II | Brigatinib | A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib (ALTA-2) | Completed | USA | SWE | NLD | ITA | FRA | ESP | DEU | CAN | AUT | AUS | 5 |
NCT05718297 | Phase II | Brigatinib Durvalumab | Brigatinib Post Definitive Chemo-radiotherapy in Patients With ALK-fusion Non-small Cell Lung Cancer (BOUNCE) | Withdrawn | POL | ITA | GBR | FRA | ESP | 0 |
NCT04318938 | Phase II | Brigatinib | Advancing Brigatinib Properties in ALK+ NSCLC Patients by Deep Phenotyping | Active, not recruiting | DEU | 0 |
NCT06522360 | Phase II | Brigatinib Brigatinib + Carboplatin + Pemetrexed Disodium | Brigatinib Plus Chemotherapy or Local Consolidation Therapy in ALK Positive Advanced Non-small Cell Lung Cancer (BrightStar-2) | Not yet recruiting | USA | 0 |
NCT03707938 | Phase I | Brigatinib | Local Consolidative Therapy and Brigatinib in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer | Active, not recruiting | USA | 0 |
NCT02094573 | Phase II | Brigatinib | A Phase 2, Multicenter, Randomized Study of AP26113 | Completed | 0 | |
NCT01449461 | Phase Ib/II | Brigatinib | A Phase 1/2 Study of the Oral ALK/EGFR Inhibitor AP26113 | Completed | 0 | |
NCT02706626 | Phase II | Brigatinib | Trial of Brigatinib After Treatment With Next-Generation ALK Inhibitors | Terminated | USA | 0 |
NCT04925609 | Phase Ib/II | Brigatinib | Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors (Briga-PED) | Recruiting | NLD | FRA | 0 |
NCT05200481 | Phase II | Brigatinib + Carboplatin + Pemetrexed Disodium Brigatinib | Study of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK) | Active, not recruiting | FRA | 0 |
NCT04374305 | Phase II | Brigatinib | Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2) (INTUITT-NF2) | Active, not recruiting | USA | 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 |
NCT04634110 | Phase II | Brigatinib | Brigatinib Before Brain Irradiation Trial (B3i Trial) | Terminated | USA | 0 |
NCT04223596 | Phase II | Brigatinib | Clinical Utility of Liquid Biopsy in Brigatinib ALK+ Patients (CUBIK) | Active, not recruiting | ESP | 0 |
NCT04591431 | Phase II | Everolimus Nivolumab Itacitinib Erlotinib Ponatinib Pemigatinib Ipatasertib Ipilimumab Cobimetinib Atezolizumab Palbociclib Entrectinib Vemurafenib Lapatinib Trastuzumab Brigatinib Alectinib Ado-trastuzumab emtansine Pertuzumab Vismodegib | The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy (ROME) | Active, not recruiting | ITA | 0 |
NCT03596866 | Phase III | Brigatinib Alectinib | A Study of Brigatinib Compared to Alectinib in Adults With Non-Small-Cell Lung Cancer (ALTA-3) | Completed | USA | SWE | ROU | ITA | HRV | GRC | FRA | ESP | DEU | CAN | AUT | ARG | 8 |
NCT03719898 | Phase II | Brigatinib | Brigatinib in Relapsed or Refractory ALK-Positive Anaplastic Large Cell Lymphoma | Withdrawn | USA | 0 |
NCT02784158 | Phase I | Brigatinib | An Expanded Access Study of Brigatinib for Patients With ALK-positive Advanced Non-Small Cell Lung Cancer | No longer available | USA | 0 |
NCT02737501 | Phase III | Brigatinib Crizotinib | ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-small Cell Lung Cancer (NSCLC) Participants (ALTA-1L) | Completed | USA | SWE | NOR | NLD | LUX | ITA | GBR | FRA | ESP | DNK | DEU | CHE | CAN | AUT | AUS | 4 |