| Molecular Profile |
Indication/Tumor Type |
Response Type |
Therapy Name |
Approval Status |
Evidence Type |
Efficacy Evidence |
References |
ALK rearrange MET amp
|
lung adenocarcinoma
|
resistant |
Alectinib
|
Clinical Study |
Actionable |
In a clinical case study, a lung adenocarcinoma patient harboring an ALK rearrangement developed resistance to Alecensa (alectinib)treatment, and subsequently was found to harbor amplification of MET (PMID: 24128725, PMID: 24518097).
|
24518097
24128725
|
ALK rearrange MET amp
|
lung adenocarcinoma
|
sensitive |
Crizotinib
|
Clinical Study |
Actionable |
In a clinical case study, a lung adenocarcinoma patient harboring an ALK rearrangement who developed resistance to Alecensa (alectinib) likely due to acquisition of MET amplification, responded well to treatment with Xalkori (crizotinib), demonstrating a radiological response after 12 days (PMID: 24128725, PMID: 24518097).
|
24128725
24518097
|
ALK G1123S ALK rearrange
|
lung adenocarcinoma
|
predicted - resistant |
Ceritinib
|
Clinical Study |
Actionable |
In a clinical 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 G1123S ALK rearrange
|
lung adenocarcinoma
|
predicted - sensitive |
Alectinib
|
Clinical Study |
Actionable |
In a clinical case study, Alecensa (alectinib) treatment resulted in rapid response in a patient with ALK-rearranged lung adenocarcinoma with an acquired an ALK G1123S mutation, whose disease had relapsed 2 years after initial response to Zykadia (ceritinib) (PMID: 26134233).
|
26134233
|
ALK amp ALK rearrange
|
non-small cell lung carcinoma
|
resistant |
Crizotinib
|
Clinical Study |
Actionable |
In a clinical case 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 amp ALK rearrange
|
non-small cell lung carcinoma
|
resistant |
Crizotinib
|
Clinical Study |
Actionable |
In a clinical case study, two non-small cell lung carcinoma patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and was found to have acquired ALK amplification (PMID: 25724526).
|
25724526
|
ALK rearrange ALK T1151dup ALK G1269A
|
non-small cell lung carcinoma
|
resistant |
Crizotinib
|
Clinical Study |
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 mut
|
non-small cell lung carcinoma
|
sensitive |
Ceritinib
|
Clinical Study |
Actionable |
In a retrospective analysis, patients with ALK-rearrangement positive non-small cell lung cancer that 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
|
ALK rearrange ALK G1202R
|
non-small cell lung carcinoma
|
predicted - resistant |
Brigatinib
|
Clinical Study |
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
|
non-small cell lung carcinoma
|
predicted - resistant |
Alectinib
|
Clinical Study |
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
|
non-small cell lung carcinoma
|
predicted - resistant |
Alectinib
|
Clinical Study |
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 I1171N MET amp
|
non-small cell lung carcinoma
|
predicted - resistant |
Brigatinib
|
Clinical Study |
Actionable |
In a clinical case study, MET amplification was identified together with a preexisting ALK I1171N 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 I1171T
|
lung adenocarcinoma
|
resistant |
Alectinib
|
Clinical Study |
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
|
non-small cell lung carcinoma
|
predicted - resistant |
Brigatinib
|
Clinical Study |
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 I1171T
|
lung adenocarcinoma
|
resistant |
Crizotinib
|
Clinical Study |
Actionable |
In a clinical case study, a patient with a lung adenocarcinoma tumor harboring an ALK rearrangement and 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
|
non-small cell lung carcinoma
|
predicted - resistant |
Alectinib
|
Clinical Study |
Actionable |
In a clinical case study, ALK I1171T was identified in the post-progression biopsy of a non-small cell lung cancer patients harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 29935304).
|
29935304
|
ALK rearrange ALK I1171N
|
non-small cell lung carcinoma
|
predicted - sensitive |
Brigatinib
|
Clinical Study |
Actionable |
In a clinical case 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 I1171N
|
non-small cell lung carcinoma
|
predicted - resistant |
Alectinib
|
Clinical Study |
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 C1156Y
|
non-small cell lung carcinoma
|
resistant |
Crizotinib
|
Clinical Study |
Actionable |
In a clinical case study, a non-small cell lung carcinoma 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 I1171N ALK L1198F
|
non-small cell lung carcinoma
|
resistant |
Lorlatinib
|
Clinical Study |
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 RB1 C706F TP53 loss
|
lung small cell carcinoma
|
predicted - resistant |
Lorlatinib
|
Clinical Study |
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
|
non-small cell lung carcinoma
|
sensitive |
Crizotinib
|
FDA approved |
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).
|
25470694
|
ALK rearrange
|
non-small cell lung 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
|
non-small cell lung 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
|
non-small cell lung 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
|
non-small cell lung 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
|
non-small cell lung carcinoma
|
sensitive |
Brigatinib
|
Clinical Study |
Actionable |
In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulted in objective response in 17% (3/18) and stable disease in 50% (9/18) of patients with alectinib-refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304).
|
29935304
|
ALK rearrange
|
non-small cell lung 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 crizotinib-treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716).
|
27836716
|
ALK rearrange
|
non-small cell lung carcinoma
|
sensitive |
Brigatinib
|
Clinical Study |
Actionable |
In a retrospective study, 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
|
non-small cell lung carcinoma
|
sensitive |
Brigatinib
|
FDA approved |
Actionable |
In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted 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 non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573).
|
28475456
|
ALK rearrange
|
non-small cell lung carcinoma
|
sensitive |
Brigatinib
|
Guideline |
Actionable |
Alunbrig (brigatinib) is included in guidelines as subsequent therapy for ALK rearranged non-small cell lung cancer patients whose disease progressed after Xalkori (crizotinib) therapy (NCCN.org).
|
detail...
|
ALK rearrange
|
non-small cell lung 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
|
non-small cell lung 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
|
non-small cell lung carcinoma
|
no benefit |
Atezolizumab
|
Clinical Study |
Actionable |
In a retrospective study, 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
|
non-small cell lung 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
|
non-small cell lung 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
|
non-small cell lung carcinoma
|
no benefit |
Pembrolizumab
|
Clinical Study |
Actionable |
In a retrospective study, 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
|
non-small cell lung carcinoma
|
no benefit |
Durvalumab
|
Clinical Study |
Actionable |
In a retrospective study, 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
|
non-small cell lung 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
|
non-small cell lung 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 (PMID: 29563138; NCT01625234).
|
29563138
|
ALK rearrange
|
non-small cell lung carcinoma
|
sensitive |
Ensartinib
|
Clinical Study |
Actionable |
In a retrospective study, 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
|
non-small cell lung 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
|
non-small cell lung carcinoma
|
sensitive |
Ceritinib
|
Guideline |
Actionable |
Zykadia (ceritinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer patients, and as subsequent therapy in patients whose disease progressed after Xalkori (crizotinib) therapy (NCCN.org).
|
detail...
|
ALK rearrange
|
non-small cell lung carcinoma
|
sensitive |
Ceritinib
|
FDA approved |
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
|
ALK rearrange
|
non-small cell lung carcinoma
|
sensitive |
Ceritinib
|
Clinical Study |
Actionable |
In a retrospective study, 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
|
non-small cell lung 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
|
non-small cell lung 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
|
Advanced Solid Tumor
|
sensitive |
Entrectinib
|
Phase I |
Actionable |
In a Phase I trial, Entrectinib (RXDX-101) 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 analyzing combined results of 2 Phase I trials, Entrectinib (RXDX-101) 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 received prior Alk inhibitor treatments (PMID: 28183697).
|
28183697
|
ALK rearrange
|
non-small cell lung 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
|
non-small cell lung carcinoma
|
no benefit |
Nivolumab
|
Clinical Study |
Actionable |
In a retrospective study, 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
|
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
|
non-small cell lung carcinoma
|
sensitive |
Alectinib
|
Guideline |
Actionable |
Alecensa (alectinib) is included in guidelines as the preferred first-line therapy for patients with ALK-rearranged, metastatic non-small cell lung cancer, and as the subsequent therapy for patients who have progressed after Xalkori (crizotinib) (NCCN.org).
|
detail...
|
ALK rearrange
|
non-small cell lung 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
|
non-small cell lung carcinoma
|
sensitive |
Alectinib
|
Clinical Study |
Actionable |
In a retrospective study, 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
|
non-small cell lung carcinoma
|
sensitive |
Alectinib
|
FDA approved |
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
|
ALK rearrange
|
non-small cell lung carcinoma
|
sensitive |
Lorlatinib
|
Phase II |
Actionable |
IIn a Phase II trial, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 90% (27/30; 1 complete response (CR) and 26 partial responses (PR)) and an intracranial response rate of 66.7% (2/3) in treatment-naive non-small cell lung cancer (NSCLC) patients harboring an ALK rearrangement, and an OR rate of 47% (93/198; 4 CR, 89 PR) and an objective intracranial response rate of 63% (51/81) in ALK-rearranged NCSLC patients that had received prior therapy (PMID: 30413378; NCT01970865).
|
30413378
|
ALK rearrange
|
non-small cell lung carcinoma
|
sensitive |
Lorlatinib
|
FDA approved |
Actionable |
In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 48% (103/215, 4% complete response, 44% partial response) in ALK-rearranged non-small cell lung carcinoma patients that had received more than one prior Alk kinase inhibitor therapy, with an estimated median response duration of 12.5 months (J Clin Oncol, May 2018, 36(no. 15_suppl):9032-9032; NCT01970865).
|
detail...
|
ALK rearrange
|
non-small cell lung 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
|
non-small cell lung carcinoma
|
sensitive |
Ceritinib + Crizotinib
|
Clinical Study |
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 ALK V1180L
|
non-small cell lung carcinoma
|
resistant |
Alectinib
|
Clinical Study |
Actionable |
In a clinical case study, ALK V1180L was identified in post-progression biopsies of 2 non-small cell lung cancer patients harboring an ALK rearrangement after disease progression on Alecensa (alectinib) treatment (PMID: 29935304).
|
29935304
|
ALK rearrange ALK V1180L
|
non-small cell lung carcinoma
|
predicted - sensitive |
Brigatinib
|
Clinical Study |
Actionable |
In a clinical case study, Alunbrig (brigatinib) treatment resulted in 1 partial response and 1 stable disease in 2 patients with Alecensa (alectinib)-refractory, ALK-rearranged non-small cell lung cancer with an acquired ALK V1180L (PMID: 29935304).
|
29935304
|
ALK rearrange ALK G1202R ALK L1196M
|
non-small cell lung carcinoma
|
resistant |
Lorlatinib
|
Clinical Study |
Actionable |
In a clinical study, ALK L1196M was identified as an acquired mutation 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 S1206Y
|
non-small cell lung carcinoma
|
resistant |
Crizotinib
|
Clinical Study |
Actionable |
In a clinical case study, a non-small cell lung carcinoma 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 S1206Y
|
non-small cell lung 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 G1202R ALK G1269A ALK L1204V
|
non-small cell lung carcinoma
|
resistant |
Lorlatinib
|
Clinical Study |
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 SRC pos
|
non-small cell lung carcinoma
|
sensitive |
Saracatinib + Ceritinib
|
Preclinical - Patient cell culture |
Actionable |
In a preclinical study, the combination of Saracatinib (AZD0530) and Zykadia (ceritinib) demonstrated efficacy in non-small cell lung cancer patient derived cells harboring an ALK fusion and upregulation of SRC in culture (PMID: 25394791).
|
25394791
|
ALK rearrange ALK E1210K ALK D1203N ALK G1269A
|
non-small cell lung carcinoma
|
resistant |
Lorlatinib
|
Clinical Study |
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 TP53 mut
|
non-small cell lung 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
|
non-small cell lung 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
|
non-small cell lung 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
|
non-small cell lung 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 L1196M
|
non-small cell lung carcinoma
|
resistant |
Crizotinib
|
Clinical Study |
Actionable |
In a clinical case study, four non-small cell lung carcinoma patients harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed, and was found to have acquired ALK L1196M (PMID: 25724526).
|
25724526
|
ALK rearrange ALK L1196M
|
non-small cell lung carcinoma
|
resistant |
Crizotinib
|
Clinical Study |
Actionable |
In a clinical case study, ALK L1196M was identified in biopsies from a non-small cell lung cancer patient harboring ALK rearrangement who developed resistance to Xalkori (crizotinib) (PMID: 22277784).
|
22277784
|
ALK rearrange ALK C1156Y ALK L1198F
|
non-small cell lung carcinoma
|
resistant |
Lorlatinib
|
Clinical Study |
Actionable |
In a clinical study, ALK D1203N was identified as an acquired mutation in an ALK-positive non-small cell lung cancer patient harboring ALK C1156Y who developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).
|
29650534
|
ALK rearrange MAP2K1 K57N
|
non-small cell lung 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 AZD6244, resulting in decreased cell survival in culture and reduced tumor volume in xenograft models (PMID: 25394791).
|
25394791
|
ALK rearrange ALK I1171N ALK D1203N
|
non-small cell lung carcinoma
|
resistant |
Lorlatinib
|
Clinical Study |
Actionable |
In a clinical study, an ALK-positive non-small cell lung cancer patient harboring ALK I1171N and D1203N in cis developed resistance to Lorlatinib (PF-06463922) after initial response (PMID: 29650534).
|
29650534
|
ALK rearrange ALK V1180L ALK L1196M ALK G1202R
|
non-small cell lung carcinoma
|
predicted - resistant |
Brigatinib
|
Clinical Study |
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
|
non-small cell lung carcinoma
|
predicted - resistant |
Brigatinib
|
Clinical Study |
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
|