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Therapy Name | Ensartinib |
Synonyms | |
Therapy Description |
Ensartinib (X-396) is a small molecule inhibitor of ALK, which inhibits downstream signaling and potentially leads to decreased growth of ALK-expressing tumors (PMID: 21613408, PMID: 31628085). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Ensartinib | X-396 | ALK Inhibitor 32 | Ensartinib (X-396) is a small molecule inhibitor of ALK, which inhibits downstream signaling and potentially leads to decreased growth of ALK-expressing tumors (PMID: 21613408, PMID: 31628085). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK E1210K | lung non-small cell carcinoma | predicted - resistant | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-small cell lung cancer progressed on Ensartinib (X-396) treatment and was found to have acquired ALK E1210K and lost ALK L1152V and G1269A in plasma cell-free DNA (PMID: 31446141). | 31446141 |
EML4 - ALK | intrahepatic cholangiocarcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response with tumor regression in a patient with metastatic intrahepatic cholangiocarcinoma harboring EML4-ALK (PMID: 37675235). | 37675235 |
EML4 - ALK ALK L1196M | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical | Actionable | In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK ALK L1196M (PMID: 21613408). | 21613408 |
EML4 - ALK ALK I1171N | lung adenocarcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, Ensartinib (X-396) treatment resulted in a decrease in the liver lesions after 20 days of treatment in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK I1171N (PMID: 36864442). | 36864442 |
EML4 - ALK ALK L1152R | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK L1152R in culture (PMID: 31446141). | 31446141 |
ALK fusion | lung non-small cell carcinoma | sensitive | Ensartinib | Phase II | Actionable | In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 57% (43/75; all partial responses), and stable disease (SD) in 33% (25/75) of patients with crizotinib-refractory non-small cell lung cancer harboring an ALK fusion, with a response rate of 59% and SD rate of 31% in the 70 patients with EML4-ALK, and a response rate of 40% and SD rate of 60% in the 5 patients with non-EML4 ALK fusions (PMID: 31628085; NCT03215693). | 31628085 |
EML4 - ALK ALK I1171N | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 36201110). | 36201110 |
ALK rearrange ALK I1171X | lung non-small cell carcinoma | predicted - resistant | Ensartinib | 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 G1123S | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK G1123S in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK C1156Y | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) 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 | Ensartinib | Preclinical | Actionable | In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK C1156Y (PMID: 21613408). | 21613408 |
ALK rearrange ALK T1151M | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a non-small cell lung cancer patient harboring a non-coding ALK rearrangement with ALK T1151M (PMID: 31446141). | 31446141 |
ALK I1171T ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569). | 31628085 |
ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Ensartinib | 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 | lung adenocarcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, neoadjuvant Ensartinib (X-396) resulted in a major pathological response and decreased tumor size allowing for resection 5 months after treatment intitation in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 36730477). | 36730477 |
EML4 - ALK ALK S1206F | lung non-small cell carcinoma | predicted - resistant | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK S1206F, along with EML4-ALK (v3), was identified in plasma cell-free DNA in a patient with non-small cell lung cancer harboring EML4-ALK (v5) who progressed on Ensartinib (X-396) treatment (PMID: 31446141). | 31446141 |
EML4 - ALK ALK L1198F | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK L1198F in culture (PMID: 31446141). | 31446141 |
EML4 - ALK | lung non-small cell carcinoma | sensitive | Ensartinib | Phase II | Actionable | In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 59% (41/70; all partial responses) and stable disease in 31% (22/70) of patients with crizotinib-refractory non-small cell lung cancer harboring EML4-ALK (PMID: 31628085; NCT03215693). | 31628085 |
ALK D1225N | lung adenocarcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring ALK D1225N (PMID: 37529699). | 37529699 |
EML4 - ALK ALK L1196M | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a non-small cell lung cancer patient harboring EML4-ALK (v5) with ALK L1196M and stable disease in another patient harboring EML4-ALK (v2) with ALK L1196M (PMID: 31446141). | 31446141 |
ALK F1174L ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) of patients with ALK-positive non-small cell lung cancer harboring ALK F1174L (n=5) or ALK F1174V (n=1) (PMID: 31628085; NCT0321569). | 31628085 |
ALK amp ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 56% (5/9, all partial responses) and stable disease in 44% (4/9) of patients with ALK-positive non-small cell lung cancer with ALK amplification (PMID: 31628085; NCT0321569). | 31628085 |
ALK L1152V ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 25% (1/4) of patients with ALK-positive non-small cell lung cancer harboring ALK L1152R (n=3) or L1152V (n=1) (PMID: 31628085; NCT0321569). | 31628085 |
ALK F1174V ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) of patients with ALK-positive non-small cell lung cancer harboring ALK F1174L (n=5) or ALK F1174V (n=1) (PMID: 31628085; NCT0321569). | 31628085 |
ALK rearrange ALK L1196M | lung non-small cell carcinoma | predicted - resistant | Ensartinib | 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 positive | lung non-small cell carcinoma | sensitive | Ensartinib | Phase II | Actionable | In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 52% (76/147; all partial responses), and disease control in 93% (137/147) of patients with crizotinib-refractory ALK-positive non-small cell lung cancer, and a median progression-free survival of 9.6 mo., and of the 97 patients with brain metastases, 41% (40) demonstrated a partial response, and of those, 28 (70%) had an intracranial response and 39 (98%) had intracranial disease control (PMID: 31628085; NCT03215693). | 31628085 |
ALK L1152V ALK G1269A | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a clinical case study, Ensartinib (X-396) treatment resulted in a partial response in a patient with non-small cell lung cancer harboring ALK L1152V and ALK G1269A (PMID: 31446141). | 31446141 |
ALK amp | neuroblastoma | predicted - sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) treatment resulted in inhibition of cell proliferation in a neuroblastoma cell line harboring ALK amplification in culture (PMID: 34482287). | 34482287 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Ensartinib | Phase III | Actionable | In a Phase III trial, Ensartinib (X-396) treatment significantly improved progression-free survival in patients with ALK-positive non-small cell lung cancer (25.8 vs 12.7 mo, HR 0.51, p<0.001) compared to Xalkori (crizotinib), and resulted in an intracranial response rate of 63.6% (7 of 11) in patients with target brain metastases at baselinewith compared to 21.1% (4 of 19) with Xalkori (crizotinib) (PMID: 34473194; NCT02767804). | 34473194 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Ensartinib | 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 Ensartinib (X-396), and radiotherapy (PMID: 26438117). | 26438117 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Ensartinib | Phase Ib/II | Actionable | In a Phase I/II trial, Ensartinib (X-396) treatment resulted in partial response in 60% (36/60) and stable disease in 21.7 % (13/60) of patients with ALK-positive non-small cell lung cancer, with a median progression-free survival of 9.2 months, and a response rate of 80% (12/15) in crizotinib-naïve patients and 69% (20/29) in patients with prior crizotinib treatment (PMID: 29563138; NCT01625234). | 29563138 |
ALK rearrange | lung non-small cell carcinoma | sensitive | Ensartinib | Guideline | Actionable | Ensartinib (X-396) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 30285222, Version Update 15 Sept 2020; ESMO.org). | detail... 30285222 |
EML4 - ALK ALK E1210K | Advanced Solid Tumor | resistant | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing EML4-ALK with ALK E1210K was resistant to Ensartinib (X-396) in culture (PMID: 31446141). | 31446141 |
ALK L1152R ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 25% (1/4) of patients with ALK-positive non-small cell lung cancer harboring ALK L1152R (n=3) or L1152V (n=1) (PMID: 31628085; NCT0321569). | 31628085 |
ALK C1156Y ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 71% (5/7, all partial responses) and stable disease in 29% (2/7) of patients with ALK-positive non-small cell lung cancer harboring ALK C1156Y (PMID: 31628085; NCT0321569). | 31628085 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK F1174V in culture (PMID: 31446141). | 31446141 |
ALK G1202R ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 33% (2/6, all partial responses) and stable disease in 50% (3/6) of patients with ALK-positive non-small cell lung cancer harboring ALK G1202R (PMID: 31628085; NCT0321569). | 31628085 |
ALK L1196M ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 25% (1/12, all partial responses) and stable disease in 67% (8/12) of patients with ALK-positive non-small cell lung cancer harboring ALK L1196M (PMID: 31628085; NCT0321569). | 31628085 |
ALK I1171S ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensartinib (X-396) treatment resulted in an objective response in 50% (2/4, all partial responses) and stable disease in 50% (2/4) of patients with ALK-positive non-small cell lung cancer harboring ALK I1171T (n=3) or I1171S (n=1) (PMID: 31628085; NCT0321569). | 31628085 |
EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Ensartinib (X-396) in culture (PMID: 36201110). | 36201110 |
EML4 - ALK ALK G1202R | Advanced Solid Tumor | resistant | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing EML4-ALK with ALK G1202R was resistant to Ensartinib (X-396) in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK G1269A | Advanced Solid Tumor | resistant | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing EML4-ALK with ALK G1269A was resistant to Ensartinib (X-396) in culture (PMID: 31446141). | 31446141 |
EML4 - ALK | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191). | 30002191 |
EML4 - ALK ALK V1180L | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 31446141). | 31446141 |
ALK R1275Q | neuroblastoma | predicted - sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensartinib (X-396) treatment resulted in inhibition of cell proliferation in a neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 34482287). | 34482287 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT02767804 | Phase III | Crizotinib Ensartinib | eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients | Active, not recruiting | USA | TUR | POL | NLD | ITA | ISR | GBR | FRA | ESP | DEU | CZE | CAN | BRA | BEL | AUS | ARG | 4 |
NCT03155620 | Phase II | Tazemetostat Larotrectinib LY3023414 Vemurafenib Palbociclib Olaparib Ulixertinib Erdafitinib Selumetinib Ensartinib | Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) | Recruiting | USA | CAN | AUS | 1 |
NCT02898116 | Phase Ib/II | Durvalumab + Ensartinib Ensartinib | A Study of ALK Inhibitor, Ensartinib, and Anti-PD-L1, Durvalumab, in Subjects With ALK-rearranged Non-small Cell Lung Cancer | Completed | USA | 0 |
NCT03213652 | Phase II | Ensartinib | Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial) | Recruiting | USA | CAN | AUS | 1 |
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 |
NCT01625234 | Phase Ib/II | Ensartinib | Phase 1/2 Study of X-396, an Oral ALK Inhibitor, in Patients With ALK-positive Non-Small Cell Lung Cancer | Completed | USA | 0 |
NCT04146571 | Expanded access | Ensartinib | Expanded Access to Ensartinib for Participants With ALK+ NSCLC | Available | USA | 0 |
NCT03420508 | Phase II | Ensartinib | Treating Patients With Melanoma and ALK Alterations With Ensartinib | Active, not recruiting | USA | 0 |