Molecular Profile |
Indication/Tumor Type |
Response Type |
Therapy Name |
Approval Status |
Evidence Type |
Efficacy Evidence |
References |
ROS1 fusion
|
Advanced Solid Tumor
|
sensitive
|
Brigatinib
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ROS1 fusion proteins in culture (PMID: 27780853).
|
27780853
|
ROS1 fusion
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate of 72% (36/50), with 3 complete responses and 33 partial responses, a median duration of response of 17.6 months, and a median progression-free survival of 19.2 months in patients with non-small cell lung cancer harboring ROS1 rearrangements as detected by an FDA-approved test (PMID: 25264305; NCT00585195).
|
detail...
25264305
detail...
|
ROS1 fusion
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
Clinical Study - Cohort |
Actionable |
In a Phase II trial (NLMT), Xalkori (crizotinib) treatment resulted in an observed objective response rate (ORR) of 71% (5/7), durable clinical benefit rate (DCBR) of 75% (6/8), and medial progression-free survival (PFS) of 44.6 months in patients with non-small cell lung cancer harboring ROS1 fusions, with Bayesian estimated OR and DCBR of 68% and 71%, respectively, and Bayesian posterior probability for OR and DCBR of 0.99 and >0.99, respectively (PMID: 32669708, NCT02664935).
|
32669708
|
ROS1 fusion
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
Phase I |
Actionable |
In a Phase I clinical trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)).
|
detail...
|
ROS1 fusion
|
Advanced Solid Tumor
|
predicted - sensitive
|
Entrectinib
|
Case Reports/Case Series |
Actionable |
In a Phase I/II trial (STARTRK-NG), Rozlytrek (entrectinib) treatment was safe and resulted in an overall response rate (ORR) of 57.7% (15/26, 7 complete responses) with median duration of response and progression-free survival no reached in pediatric patients with CNS or extracranial solid tumors harboring fusions in NTRK1, NTRK2, NTRK3, ROS1, or ALK, ORR was 62.5% (5/8) in patients harboring ROS1 fusions (PMID: 35395680; NCT02650401).
|
35395680
|
ROS1 fusion
|
lung non-small cell carcinoma
|
unknown
|
unspecified immune checkpoint inhibitor
|
Clinical Study - Cohort |
Actionable |
In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was not reached in a patient harboring ROS1 fusion, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448).
|
30268448
|
ROS1 fusion
|
lung non-small cell carcinoma
|
sensitive
|
Entrectinib
|
FDA approved |
Actionable |
In a combined analysis of 3 clinical trials (ALKA-372-001, STARTRK-1, STARTRK-2) that supported FDA approval, Rozlytrek (entrectinib) treatment resulted in an objective response rate of 77% (41/53), a median duration of response of 25 months in patients with ROS1 fusion positive non-small cell lung cancer, with median progression-free survival of 26 and 14 months for patients without (n=30) and with (n=23) CNS disease, respectively (PMID: 31838015; NCT02097810; NCT02568267).
|
detail...
31838015
|
ROS1 fusion
|
Advanced Solid Tumor
|
predicted - sensitive
|
Repotrectinib
|
Phase I |
Actionable |
In a Phase I (TRIDENT-1) trial, Repotrectinib (TPX-0005) treatment resulted in partial response in 21.6% (8/37) of patients with advanced solid tumors harboring ROS1 or NTRK fusions (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116).
|
detail...
|
ROS1 fusion
|
lung non-small cell carcinoma
|
predicted - sensitive
|
DS6051b
|
Phase I |
Actionable |
In a Phase I clinical trial, DS-6051b was well-tolerated and demonstrated some preliminary efficacy in patients with advanced solid tumors, including a partial response in a patient with non-small cell lung cancer liver metastases harboring a ROS1 fusion (Cancer Res July 15 2016 (76) (14 Supplement) CT024).
|
detail...
|
ROS1 rearrange
|
lung adenocarcinoma
|
sensitive
|
Crizotinib
|
Phase I |
Actionable |
In a retrospective analysis of Phase I clinical data, Xalkori (crizotinib) resulted in an objective response rate of 80% (24/30) and a median PFS of 9.1 months in patients with ROS1 rearranged lung adenocarcinoma (PMID: 25667280).
|
25667280
|
ROS1 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 ROS1 rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).
|
detail...
|
ROS1 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 ROS1 rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).
|
detail...
|
ROS1 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 ROS1 rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).
|
detail...
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
Phase II |
Actionable |
In a Phase II clinical trial, patients with non-small cell lung cancer harboring a ROS1 rearrangement demonstrated an objective response rate of 70% (21/30; all partial response), a median progression-free survival (PFS) of 20 months, a duration of response of 19 months, and a survival rate of 83% at 12 months and 63% at 24 months, when treated with Xalkori (crizotinib) (PMID: 30978502; NCT02183870).
|
30978502
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
Guideline |
Actionable |
Xalkori (crizotinib) is included in guidelines as the preferred first-line therapy for ROS1 rearranged non-small cell lung cancer (NCCN.org).
|
detail...
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
FDA approved - On Companion Diagnostic |
Actionable |
In a Phase I trial (PROFILE 1001) that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate of 72% (38/53), with 6 complete responses and 32 partial responses, a median duration of response of 24.7 months, a median progression-free survival of 19.3 months, and a median overall survival of 51.4 months in patients with non-small cell lung cancer harboring ROS1 rearrangements as detected by an FDA-approved test (PMID: 30980071; NCT00585195).
|
detail...
detail...
30980071
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Crizotinib
|
Phase II |
Actionable |
In a Phase II trial (AcSe), treatment with Xalkori (crizotinib) resulted in a an overall response rate after 2 cycles of 47.2% (17/36; all partial responses), and after 4 cycles resulted in a best overall response rate of 69.4% (21/36; 20 partial responses and 1 complete response), and a median progression-free survival of 5.5 months and median overall survival of 17.2 months in patients with ROS1-translocated non-small cell lung cancer (PMID: 31584608; NCT02034981).
|
31584608
|
ROS1 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 a ROS1 rearrangement, or as a next-line therapy in patients with ROS1-rearranged non-small cell lung cancer who have not received prior Xalkori (crizotinib) therapy (PMID: 32169226; ESMO.org).
|
detail...
32169226
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
predicted - sensitive
|
DS6051b
|
Phase I |
Actionable |
In a Phase I trial, DS6051b demonstrated manageable toxicity, resulted in an objective response rate of 33.3% (2/6) in patients with advanced non-small cell lung cancer harboring ROS1 rearrangements (PMID: 32591465).
|
32591465
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Repotrectinib
|
Guideline |
Actionable |
Repotrectinib (TPX-0005) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring a ROS1 rearrangement, or as a next-line therapy in patients with ROS1-rearranged non-small cell lung cancer who have not received prior ROS1 inhibitor therapy (PMID: 32169226, Version Update 15 Sept 2020; ESMO.org).
|
detail...
32169226
|
ROS1 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 ROS1 rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org).
|
detail...
|
ROS1 rearrange
|
Advanced Solid Tumor
|
sensitive
|
Entrectinib
|
Phase I |
Actionable |
In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in complete response in 13% (1/12) and objection response in 75% (6/8) of patients with advanced solid tumors harboring rearrangement in ROS1 gene (AACR Apr 2016, Abstract # CT007).
|
detail...
|
ROS1 rearrange
|
Advanced Solid Tumor
|
sensitive
|
Entrectinib
|
Phase I |
Actionable |
In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) treatment to result in an objective response rate of 86% (12/14) in patients with ROS-1 rearranged advanced solid tumors that were treatment-naive, but no response (0/6) in patients who received prior Xalkori (crizotinib) (PMID: 28183697).
|
28183697
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
no benefit
|
Alectinib
|
Guideline |
Actionable |
Alecensa (alectinib) is not indicated for use in ROS1 rearranged non-small cell lung cancer patients whose disease became resistant to Xalkori (crizotinib) (NCCN.org).
|
detail...
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Ceritinib
|
Guideline |
Actionable |
Zykadia (ceritinib) is included in guidelines as first-line therapy for ROS1-rearranged non-small cell lung cancer, but is not indicated after patients become resistant to Xalkori (crizotinib) (NCCN.org).
|
detail...
|
ROS1 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 a ROS1 rearrangement who have not received prior Xalkori (crizotinib) therapy (PMID: 32169226; ESMO.org).
|
detail...
32169226
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Ceritinib
|
Phase II |
Actionable |
In a Phase II trial, treatment with Zykadia (ceritinib) resulted in an overall response rate of 62% (20/32, including 1 complete response), a disease control rate of 81% (26/32), and a progression-free survival of 9.3 months in all patients and 19.3 months in Xalkori (crizotinib)-naive patients with non-small cell lung cancer harboring a ROS1 rearrangement (PMID: 28520527; NCT01964157).
|
28520527
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
WX-0593
|
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 44.4% (4/9) and DCR of 66.7% (6/9) in patients with a ROS1 rearrangement (PMID: 35087031).
|
35087031
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
no benefit
|
Brigatinib
|
Guideline |
Actionable |
Alunbrig (brigatinib) is not indicated for use in ROS1 rearranged non-small cell lung cancer patients whose disease became resistant to Xalkori (crizotinib) (NCCN.org).
|
detail...
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
no benefit
|
Brigatinib
|
Case Reports/Case Series |
Actionable |
In a retrospective analysis, Alunbrig (brigatinib) treatment resulted in a partial response in a patient with Xalkori (crizotinib)-naive non-small cell lung cancer (NSCLC) harboring ROS1 rearrangement, and resulted in 1 partial response and 1 stable disease in 7 patients with Xalkori (crizotinib)-resistant NSCLC harboring ROS1 rearrangements (PMID: 32462394).
|
32462394
|
ROS1 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 50% (6/12) of patients with non-small cell lung carcinoma harboring a ROS1 rearrangement (PMID: 29074098; NCT03052608).
|
29074098
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
Guideline |
Actionable |
Lorbrena (lorlatinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring a ROS1 rearrangement, or as a next-line therapy in patients with ROS1-rearranged non-small cell lung cancer who have not received prior ROS1 inhibitor therapy (PMID: 32169226, Version Update 15 Sept 2020; ESMO.org).
|
32169226
detail...
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
Phase Ib/II |
Actionable |
In a Phase I/II trial, Lorbrena (lorlatinib) treatment resulted in an objective response rate of 62% (13/21) in tyrosine kinase inhibitor (TKI)-naive and 35% (14/40) in previous Xalkori (crizotinib)-treated patients with non-small cell lung cancer harboring ROS1 rearrangements, intracranial responses were observed in 64% (7/11) of TKI-naive patients and 50% (12/24) of previous Xalkori (crizotinib)-treated patients (PMID: 31669155; NCT01970865).
|
31669155
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Lorlatinib
|
Guideline |
Actionable |
Lorbrena (lorlatinib) is included in guidelines as subsequent therapy in patients with advanced or metastatic ROS1-rearranged non-small lung cancer (NCCN.org).
|
detail...
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Entrectinib
|
Guideline |
Actionable |
Rozlytrek (entrectinib) is included in guidelines as a preferred therapy for patients with advanced or metastatic ROS1 rearrangement-positive non-small cell lung cancer (NCCN.org).
|
detail...
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Entrectinib
|
Phase I |
Actionable |
In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) treatment to result in complete response in 15% (2/13) and partial response in 77% (10/13) patients with ROS-1 rearranged non-small cell lung carcinoma that were treatment-naive (PMID: 28183697).
|
28183697
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
Entrectinib
|
Guideline |
Actionable |
Rozlytrek (entrectinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring a ROS1 rearrangement, or as a next-line therapy in patients with ROS1-rearranged non-small cell lung cancer who have not received prior ROS1 inhibitor therapy (PMID: 32169226, Version Update 15 Sept 2020; ESMO.org).
|
32169226
detail...
|
ROS1 rearrange
|
lung non-small cell carcinoma
|
sensitive
|
NPS-1034
|
Preclinical - Cell culture |
Actionable |
In a preclinical study, NPS-1034 inhibited ROS1 activity and proliferation of a non-small cell lung cancer cell line harboring a ROS1 rearrangement in culture (PMID: 24165158).
|
24165158
|