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| Gene | ALK |
| Variant | rearrange |
| Impact List | unknown |
| Protein Effect | unknown |
| Gene Variant Descriptions | ALK rearrangement indicates an unspecified rearrangement of the ALK gene. |
| Associated Drug Resistance |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ALK rearrange | lung non-small cell carcinoma | no benefit | Ipilimumab + Nivolumab | Guideline | Actionable | Immune checkpoint inhibitors including Keytruda (pembrolizumab), Tecentriq (atezolizumab), and the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) are not indicated for use as initial systemic therapy in non-small cell lung cancer patients harboring oncogenes, including ALK rearrangement (NCCN.org). | detail... |
| ALK rearrange | lung adenocarcinoma | predicted - sensitive | CT-707 | Phase I | Actionable | In a Phase I trial, Conteltinib (CT-707) demonstrated safety and preliminary efficacy, resulting in an overall response rate of 77% (10/13, 1 complete response, 9 partial responses) and a disease control rate of 85% (11/13) in patients with ALK-rearranged lung adenocarcinoma (n=12) or malignant pleural mesothelioma (n=1), median progression-free survival was 13 months in patients with lung adenocarcinoma (PMID: 32181989). | 32181989 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Alectinib | 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 Alecensa (alectinib), and radiotherapy (PMID: 26438117). | 26438117 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Alectinib | Guideline | Actionable | Alecensa (alectinib) is included in guidelines as the preferred first-line therapy and as subsequent therapy for patients with ALK-rearranged advanced or metastatic non-small cell lung cancer (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Alectinib | Guideline | Actionable | Alecensa (alectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 31987360, PMID: 30285222; ESMO.org). | 31987360 30285222 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Alectinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangement (PMID: 28586279; NCT02075840). | 28586279 detail... detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Alectinib | Phase II | Actionable | In a Phase II trial, Alecensa (alectinib) treatment was effective in treating non-small cell lung cancer patients with ALK rearrangement, resulting in a 50% (61/122) objective response rate (ORR) in all patients, a 45% (43/96) ORR in Crizotinib-refractory patients, and an 83% (70/84) CNS disease control rate (PMID: 26598747). | 26598747 |
| ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Ceritinib | Guideline | Actionable | Zykadia (ceritinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). | detail... |
| ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). | detail... |
| ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a Phase I/II trial, Xalkori (crizotinib) treatment was well-tolerated and resulted in a partial response in 3 of 7 pediatric patients with ALK-rearranged inflammatory myofibroblastic tumors, and 3 of the 7 patients achieved stable disease (PMID: 23598171; NCT00939770). | 23598171 |
| ALK rearrange | malignant pleural mesothelioma | no benefit | CT-707 | Case Reports/Case Series | Actionable | In a Phase I trial, Conteltinib (CT-707) treatment resulted in disease progression after 1 cycle in a patient with ALK-rearranged malignant pleural mesothelioma (PMID: 32181989). | 32181989 |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Nivolumab | Guideline | Actionable | Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Nivolumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). | 27225694 |
| ALK rearrange | lung non-squamous non-small cell carcinoma | sensitive | Ceritinib | Phase III | Actionable | In a Phase III trial, first-line treatment with Zykadia (ceritinib) resulted in an improved median progression-free survival of 16.6 months, compared to 8.1 months with chemotherapy, in patients with ALK-rearranged non-squamous non-small cell lung cancer (PMID: 28126333; NCT01828099). | 28126333 |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Gefitinib | Guideline | Actionable | EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). | detail... |
| ALK rearrange | anaplastic large cell lymphoma | sensitive | Crizotinib | FDA approved | Actionable | In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). | 28787259 detail... |
| ALK rearrange | anaplastic large cell lymphoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). | detail... |
| 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, Lorbrena (lorlatinib) treatment significantly improved 12-month progression-free survival rate (78% vs 39%, HR 0.28, p<0.001) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer who had no prior systemic therapy, objective response rate was 82% (57/69) with 71% achieved complete intracranial response in patients with brain metastasis (PMID: 33207094; NCT03052608). | 33207094 detail... detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Lorlatinib | Guideline | Actionable | Lorbrena (lorlatinib) is included in guidelines as first-line therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer, and as subsequent therapy in patients who have progressed on Xalkori (crizotinib) and Alecensa (alectinib), Alunbrig (brigatinib), or Zykadia (ceritinib), or on Alecensa (alectinib), Alunbrig (brigatinib), or Zykadia (ceritinib) (NCCN.org). | 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 a second-generation ALK tyrosine kinase inhibitor (PMID: 31987360, PMID: 30285222; ESMO.org). | 30285222 detail... 31987360 |
| 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 | 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 | Ceritinib + Crizotinib | Clinical Study - Cohort | Actionable | In a retrospective analysis of patients with ALK-rearrangement positive non-small cell lung cancer, the combined median progression-free survival for sequential treatment with Xalkori (crizotinib) and Zykadia (ceritinib) without intervening treatments was 17.0 months, and overall survival was 49.4 months (PMID: 25724526). | 25724526 |
| ALK rearrange | Advanced Solid Tumor | sensitive | Entrectinib | Phase I | Actionable | In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in objective response in 67% (4/6) of patients with advanced solid tumors harboring rearrangement in ALK gene (AACR Apr 2016, Abstract # CT007). | detail... |
| ALK rearrange | Advanced Solid Tumor | sensitive | Entrectinib | Phase I | Actionable | In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) treatment resulted in an objective response rate of 57% (4/7) in patients with ALK rearranged advanced solid tumors that were treatment-naive, but no response (0/19) in patients who received prior Alk inhibitor treatments (PMID: 28183697). | 28183697 |
| ALK rearrange | Advanced Solid Tumor | sensitive | Belizatinib | Phase Ib/II | Actionable | In a Phase I trial, Belizatinib (TSR-011) treatment resulted in a response in 100% (3/3) of patients with ALK-rearranged advanced solid tumors when administered at higher doses, and stable disease for 7 months or longer in 56% (5/9) of patients at a lower dose (J Clin Oncol 33, 2015 (suppl; abstr 8063)). | detail... |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Osimertinib | Guideline | Actionable | EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (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 | 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 | 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 | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 31987360, PMID: 30285222; ESMO.org). | detail... 31987360 30285222 |
| 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 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 | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines as first-line and 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 | 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 | 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 | 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 | no benefit | Crizotinib + Onalespib | Phase II | Actionable | In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). | detail... |
| ALK rearrange | Advanced Solid Tumor | sensitive | ASP3026 | Phase I | Actionable | In a Phase I trial, ASP3026 treatment resulted in a partial response in 50% (8/16) and stable disease in 44% (7/16) of patients with an advanced solid tumor harboring an ALK rearrangement or ALK F1174L (PMID: 26966027; NCT01284192). | 26966027 |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Erlotinib | Guideline | Actionable | EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). | 27225694 |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Pembrolizumab | Guideline | Actionable | Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). | detail... |
| ALK rearrange | inflammatory myofibroblastic tumor | sensitive | Brigatinib | Guideline | Actionable | Alunbrig (brigatinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). | detail... |
| ALK rearrange | lung adenocarcinoma | predicted - sensitive | Bevacizumab + Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a lung adenocarcinoma patient with brain metastasis harboring an ALK rearrangement, who had progressed on single agent Lorbrena (lorlatinib) treatment, demonstrated a partial response when treated with a combination of Lorbrena (lorlatinib) and Avastin (bevacizumab), with a 68% decrease in tumor size in the brain and a total duration of disease control for 9.1 months (PMID: 33283131). | 33283131 |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Belizatinib | Phase I | Actionable | In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). | 31217479 |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Afatinib | Guideline | Actionable | EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | predicted - sensitive | PLB1003 | Phase I | Actionable | In a Phase Ia trial, PLB1003 demonstrated safety and preliminary efficacy, resulted in a disease control rate of 86% (12/14, 10 partial response, 2 stable disease) in patients with ALK-rearranged non-small cell lung cancer who progressed on or did not tolerate previous treatment (Journal of Thoracic Oncology, Volume 14, Issue 10, S651). | detail... |
| ALK rearrange | anaplastic large cell lymphoma | not applicable | N/A | Guideline | Prognostic | The presence of ALK rearrangement is associated with a favorable prognosis in patients with anaplastic large cell lymphoma (NCCN.org). | detail... |
| ALK rearrange | anaplastic large cell lymphoma | not applicable | N/A | Guideline | Diagnostic | ALK rearrangement aids in the diagnosis of anaplastic large cell lymphoma (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Ceritinib | Guideline | Actionable | Zykadia (ceritinib) is included in guidelines as 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 | Ceritinib | Guideline | Actionable | Zykadia (ceritinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 31987360, PMID: 30285222; ESMO.org). | detail... 30285222 31987360 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Ceritinib | Phase II | Actionable | In a Phase II trial (ASCEND-2), non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement and previously treated with Xalkori (crizotinib) and chemotherapy demonstrated an overall response rate of 38.6% (54/140), a disease control rate of 77.1%, a median time to response of 1.8 months, a median duration of response of 9.7 months, and a median progression-free survival of 5.7 months when treated with Zykadia (ceritinib) (PMID: 27432917; NCT01685060). | 27432917 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Ceritinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated a median overall survival of 49.5 months following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Zykadia (ceritinib), and radiotherapy (PMID: 26438117). | 26438117 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Ceritinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516). | 25754348 detail... detail... |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Atezolizumab | Guideline | Actionable | Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Atezolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). | 27225694 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Phase III | Actionable | In a Phase III trial (PROFILE 1014), Xalkori (crizotinib) treatment resulted in improved progression-free survival (PFS) (PFS=10.9 months, n=172) relative to chemotherapy (PFS=7.0 months, n=171) in NSCLC patients with ALK rearrangements, including patients with and without brain metastases at baseline, and improved intracranial disease rate in patients with brain metastases at baseline (PMID: 27022118; NCT01154140). | 27022118 |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement, or as a next-line therapy in patients with ALK-rearranged non-small cell lung cancer who have not received prior (PMID: 31987360, PMID: 30285222; ESMO guidelines). | 30285222 31987360 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Phase III | Actionable | In a Phase III trial, Xalkori (crizotinib) treatment resulted in improved objective response (87.5%, 90/103 vs 45.6%, 47/103) and median progression free survival (11.1 vs 6.8 mo) compared to pemetrexed, cisplatin and carboplatinin combination treatment in treatment-naive ALK positive advanced non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9058); NCT01639001). | detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). | detail... 25470694 detail... |
| ALK rearrange | lung non-small cell carcinoma | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as first-line and subsequent therapy for ALK rearranged non-small cell lung cancer (NCCN.org). | detail... |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Durvalumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Imfinzi (durvalumab), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). | 27225694 |
| ALK rearrange | lung non-small cell carcinoma | no benefit | Durvalumab | Guideline | Actionable | Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). | detail... |
| ALK rearrange ALK I1171T | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK I1171T was identified in the post-progression biopsy of a non-small cell lung cancer patient harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). | 29935304 |
| ALK rearrange ALK I1171T | lung adenocarcinoma | resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Alecensa (alectinib) therapy after 4 months and resistance was confirmed using cell culture with cells derived from the patient’s tumor (PMID: 25228534). | 25228534 |
| ALK rearrange ALK I1171T | lung adenocarcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement with ALK I1171T progressed on Xalkori (crizotinib) therapy after 8 months and resistance was confirmed using cell culture with cells derived from the patient's tumor (PMID: 25228534). | 25228534 |
| 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 |
| 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 |
| ALK rearrange ALK C1156Y | lung adenocarcinoma | sensitive | Lorlatinib + Saracatinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Saracatinib (AZD0530) and Lorbrena (lorlatinib) synergistically inhibited viability of cells derived from the tumor from a patient with lung adenocarcinoma harboring ALK rearrangement and an acquired ALK C1156Y in culture (PMID: 31585938). | 31585938 |
| ALK rearrange ALK C1156Y | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 18.2 months, and was found to have acquired ALK C1156Y (PMID: 25724526). | 25724526 |
| 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 MAP2K1 K57N | lung non-small cell carcinoma | sensitive | Ceritinib + Selumetinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NSCLC patient derived cells harboring an ALK rearrangement demonstrated resistance to Zykadia (ceritinib) due to the acquired mutation MAP2K1 K57N, however, sensitivity was restored to Zykadia (ceritinib) with the addition of Koselugo (selumetinib), resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791). | 25394791 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Ceritinib | 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 |
| 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 |
| 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 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK G1202R was identified in 28% (8/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). | 31358542 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Zykadia (ceritinib) followed by Alecensa (alectinib) therapy (PMID: 28285684). | 28285684 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1202R was identified in a patient with ALK-rearranged non-small cell lung carcinoma after the disease progressed while on Xalkori (crizotinib) followed by Alecensa (alectinib) therapy (PMID: 27130468). | 27130468 |
| ALK rearrange ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Alectinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK G1202R was identified in 37% (17/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). | 31358542 |
| 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 |
| ALK rearrange ALK I1171N | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a de novo ALK I1171N mutation was identified in the liver metastasis site and circulating DNA of a non-small cell lung cancer patient harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 27565911). | 27565911 |
| 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 |
| ALK rearrange ALK G1123S | lung adenocarcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, Alecensa (alectinib) treatment resulted in rapid response in a patient with ALK-rearranged lung adenocarcinoma with an acquired ALK G1123S mutation, whose disease had relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). | 26134233 |
| ALK rearrange ALK G1123S | lung adenocarcinoma | predicted - resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1123S was identified as an acquired mutation in a patient with ALK-rearranged lung adenocarcinoma whose disease relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233). | 26134233 |
| ALK rearrange ALK T1151dup ALK G1269A | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement demonstrated a partial response with Xalkori (crizotinib) treatment, but then progressed after 10.8 months, and was found to harbor secondary resistance mutations, ALK T1151dup and ALK G1269A (PMID: 25724526). | 25724526 |
| ALK rearrange ALK amp | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, three patients with non-small cell lung carcinoma co-harboring an ALK rearrangement and ALK amplification demonstrated resistance to Xalkori (crizotinib) treatment (PMID: 27432227). | 27432227 |
| ALK rearrange ALK amp | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a retrospective analysis, two non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK amplification (PMID: 25724526). | 25724526 |
| ALK rearrange ALK L1196M | lung non-small cell carcinoma | predicted - resistant | Alectinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK L1196M was identified in 22% (10/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). | 31358542 |
| 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 rearrange ALK L1196M | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a retrospective analysis, four non-small cell lung cancer patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and were found to have acquired ALK L1196M (PMID: 25724526). | 25724526 |
| ALK rearrange ALK L1196M | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring an ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784). | 22277784 |
| ALK rearrange ALK L1196M | lung non-small cell carcinoma | predicted - resistant | Ceritinib | 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 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 ALK L1196M | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK L1196M was identified in 38% (11/29) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Lorbrena (lorlatinib) treatment (PMID: 31358542). | 31358542 |
| ALK rearrange ALK L1196M | lung adenocarcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in disease progression after 4 months of therapy in a patient with ALK rearranged lung adenocarcinoma, ALK L1196M was detected in the biopsies at disease progression (PMID: 31585938). | 31585938 |
| ALK rearrange ALK S1206Y | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK S1206Y in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). | 22277784 |
| ALK rearrange ALK S1206Y | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 32 months, and was found to have acquired ALK S1206Y (PMID: 25724526). | 25724526 |
| 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 |
| 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 |
| 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 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 ALK L1196M developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534). | 29650534 |
| 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 |
| 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 |
| 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 |
| ALK rearrange ALK V1180L | lung non-small cell carcinoma | predicted - resistant | Alectinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK V1180L was identified in 11% (5/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). | 31358542 |
| ALK rearrange ALK V1180L | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK V1180L was identified in post-progression biopsies of 2 non-small cell lung cancer patients harboring an ALK rearrangement after Alecensa (alectinib) treatment (PMID: 29935304). | 29935304 |
| 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 |
| 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 |
| 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 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Alectinib | 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 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Ceritinib | 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), and a lower median overall survival with treatment with Zykadia (ceritinib) after Xalkori (crizotinib) of 7.0 mo. vs. 50.0 mo. in patients with wild-type TP53 (p=0.001) (PMID: 30165392). | 30165392 |
| 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 |
| ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Crizotinib | 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 Xalkori (crizotinib) as a first line therapy or after chemotherapy vs. patients with wild-type TP53 (5.0 mo., n=22 vs. 14.0 mo., n=71; p<0.001), and a lower median overall survival (17.0 mo., n=13 vs. not reached n=50; p=0.049) (PMID: 30165392). | 30165392 |
| ALK rearrange ALK E1210K | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer demonstrated disease progression when treated with Xalkori (crizotinib) due to a secondary acquired resistance mutation, ALK E1210K (PMID: 27432227). | 27432227 |
| ALK rearrange ALK I1171X | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK I1171X 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 rearrange ALK I1171X | lung non-small cell carcinoma | predicted - resistant | Ceritinib | 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 |
| 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 |
| 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 |
| ALK rearrange ALK I1171X | lung non-small cell carcinoma | predicted - resistant | Alectinib | Clinical Study - Cohort | Actionable | In a retrospective study, ALK I1171X was identified in 26% (12/46) of plasma samples at disease progression in ALK-positive non-small cell lung cancer patients who received Alecensa (alectinib) treatment (PMID: 31358542). | 31358542 |
| ALK rearrange ALK L1152R | lung adenocarcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule following progression on Xalkori (crizotinib) and Zykadia (ceritinib), and was subsequently treated with Alecensa (alectinib), resulting in a partial response in all disease areas (PMID: 27091190). | 27091190 |
| ALK rearrange ALK L1152R | lung adenocarcinoma | predicted - resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged lung adenocarcinoma, which also harbored RB1 deletion and TP53 G154V and R158C mutations, demonstrated a partial response following treatment with Zykadia (ceritinib), however, progressed after 4 months and was found to have an acquired ALK L1152R mutation in a biopsy of a pleural nodule (PMID: 27091190). | 27091190 |
| 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 rearrange ALK F1174L | lung adenocarcinoma | predicted - resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK F1174L was identified in biopsies at disease progression after 4 months of Zykadia (ceritinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement (PMID: 31585938). | 31585938 |
| 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 |
| 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 |
| 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 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 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 ALK L1196M ALK D1203N | lung adenocarcinoma | predicted - resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, Zykadia (ceritinib) treatment resulted in disease progression after 5 months of therapy in a patient with lung adenocarcinoma harboring ALK rearrangement and an acquired ALK L1196M, ALK D1203N was detected in the biopsies at disease progression (PMID: 31585938). | 31585938 |
| ALK rearrange ALK G1269A | lung adenocarcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK G1269A was identified in biopsies at disease progression after 30 months of Xalkori (crizotinib) treatment in a patient with lung adenocarcinoma harboring ALK rearrangement (PMID: 31585938). | 31585938 |
| ALK rearrange ALK mut | lung non-small cell carcinoma | sensitive | Ceritinib | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with ALK-rearrangement positive non-small cell lung cancer who acquired ALK drug resistance mutations following Xalkori (crizotinib) treatment had a median progression-free survival (mPFS) of 5.4 months on Zykadia (ceritinib), which was not significantly different than the mPFS of 6.5 months for patients without ALK mutations (PMID: 25724526). | 25724526 |