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
|
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
|
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 Xalkori (crizotinib) (PMID: 32169226; ESMO.org).
|
32169226
detail...
|
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
|
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
|
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
|
Guideline |
Actionable |
Xalkori (crizotinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer (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
|
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
|
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
|
inflammatory myofibroblastic tumor
|
sensitive
|
Lorlatinib
|
Guideline |
Actionable |
Lorbrena (lorlatinib) 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 clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 40 months in a pediatric patient with an ALK-rearranged inflammatory myofibroblastic tumor (PMID: 34036223).
|
34036223
|
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
|
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
|
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
|
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-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
|
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
|
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
|
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
|
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
|
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
|
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
|
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
|
Guideline |
Actionable |
Zykadia (ceritinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226; ESMO.org).
|
32169226
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
|
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
|
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
|
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 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
|
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
|
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: 32169226; ESMO.org).
|
32169226
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
|
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
|
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
|
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
|
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: 32169226, Version Update 15 Sept 2020; ESMO.org).
|
32169226
detail...
|
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
|
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
|
anaplastic large cell lymphoma
|
sensitive
|
Alectinib
|
Guideline |
Actionable |
Alecensa (alectinib) 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
|
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
|
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 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
|
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
|
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
|
sensitive
|
Alectinib
|
Guideline |
Actionable |
Alecensa (alectinib) is included in guidelines as 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
|
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
|
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
|
Guideline |
Actionable |
Alecensa (alectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226; ESMO.org).
|
32169226
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
|
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 preferred first-line therapy and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org).
|
detail...
|
ALK rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
Guideline |
Actionable |
Lorbrena (lorlatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement who have progressed on an ALK tyrosine kinase inhibitor (PMID: 32169226; ESMO.org).
|
detail...
32169226
|
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
|
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
|
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
|
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).
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detail...
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ALK rearrange
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lung adenocarcinoma
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predicted - sensitive
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Bevacizumab + Lorlatinib
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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).
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33283131
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ALK rearrange
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lung non-small cell carcinoma
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no benefit
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Nivolumab
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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).
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detail...
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ALK rearrange
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lung non-small cell carcinoma
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no benefit
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Nivolumab
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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).
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27225694
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ALK rearrange
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inflammatory myofibroblastic tumor
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sensitive
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Ceritinib
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Guideline |
Actionable |
Zykadia (ceritinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org).
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detail...
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ALK rearrange
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inflammatory myofibroblastic tumor
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sensitive
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Ceritinib
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Phase I |
Actionable |
In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 70% (7/10; 7 partial responses) and a disease control rate of 80% (8/10) in pediatric patients with inflammatory myofibroblastic tumor harboring ALK rearrangement, with median progression-free survival unreached (PMID: 34780709; NCT01742286).
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34780709
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ALK rearrange
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lung non-small cell carcinoma
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predicted - sensitive
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Ceritinib + Ribociclib
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Phase Ib/II |
Actionable |
In a Phase I/II trial, Zykadia (ceritinib) and Kisqali (ribociclib) combination therapy demonstrated a manageable safety profile and resulted in an overall response rate of 37.0% (10/27; 1 complete response and 9 partial responses) with a median progression-free survival of 21.5 months in patients with advanced ALK-rearranged non-small cell lung cancer (PMID: 35298959).
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35298959
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ALK rearrange
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lung small cell carcinoma
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predicted - sensitive
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Alectinib + Irinotecan
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Case Reports/Case Series |
Actionable |
In a clinical case study, treatment with the combination of Alecensa (alectinib) and Camptosar (irinotecan) resulted in a partial response with progression-free survival lasting longer than 6 months in a small cell lung carcinoma patient harboring an ALK rearrangement (PMID: 34729013).
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34729013
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ALK rearrange
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lung non-small cell carcinoma
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sensitive
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WX-0593
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Phase I |
Actionable |
In a Phase I trial, WX-0593 (iruplinalkib) demonstrated safety and resulted in an objective response rate (ORR) of 56.6% (56/99; all partial responses) and a disease control rate (DCR) of 83.8% (83/99), and median duration of response and median progression-free survival were not reached in non-small cell lung cancer patients with an ALK or ROS1-rearrangement, with an ORR of 58.2% (53/91; all partial responses) and DCR of 85.7% (78/91) in patients with an ALK rearrangement (PMID: 35087031; NCT03389815).
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35087031
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ALK rearrange
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lung non-small cell carcinoma
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no benefit
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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).
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detail...
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ALK rearrange
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epithelioid inflammatory myofibroblastic sarcoma
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predicted - sensitive
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Alectinib
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Case Reports/Case Series |
Actionable |
In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response lasting 44.2 months in a pediatric patient with an ALK-rearranged epithelioid inflammatory myofibroblastic tumor (PMID: 34036223).
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34036223
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ALK rearrange
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anaplastic large cell lymphoma
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predicted - sensitive
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Ceritinib
|
Phase I |
Actionable |
In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 75% (6/8; 2 complete responses, 4 partial responses) and a disease control rate of 88% (7/8) in pediatric patients with anaplastic large cell lymphoma harboring ALK rearrangement, with median progression-free survival unreached (PMID: 34780709; NCT01742286).
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34780709
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ALK mutant
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lung non-small cell carcinoma
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no benefit
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Crizotinib + Onalespib
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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).
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detail...
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ALK mutant
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lung non-small cell carcinoma
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no benefit
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Belizatinib
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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).
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31217479
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