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| Gene | ROS1 |
| Variant | rearrange |
| Impact List | unknown |
| Protein Effect | unknown |
| Gene Variant Descriptions | ROS1 rearrange indicates an unspecified rearrangement of the ROS1 gene. |
| Associated Drug Resistance |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 | 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 | 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 | 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 | 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 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 | 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 | 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 | 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 | 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 | 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 | 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 | predicted - sensitive | Taletrectinib | Phase I | Actionable | In a Phase I trial, Taletrectinib (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 | 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 | 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 | 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 |
| 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 | 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 | 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 | 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 | predicted - sensitive | TQ-B3101 | Case Reports/Case Series | Actionable | In a Phase I trial, TQ-B3101 treatment was well tolerated and resulted in an objective response rate (ORR) of 62.5% (15/24) in patients with ALK-positive, ROS1-positive, or MET-amplified advanced solid tumors, with an ORR of 62.5% (5/8) in patients with brain metastases (J Clin Oncol 38, 2020 (suppl 15; abstr e21705); NCT03019276). | detail... |
| 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 TP53 mut | lung non-small cell carcinoma | predicted - sensitive | Crizotinib | Clinical Study - Cohort | Actionable | In a Phase II clinical trial, treatment with Xalkori (crizotinib) demonstrated a shorter median progression-free survival in patients with non-small cell lung cancer co-harboring a ROS1 rearrangement and TP53 mutation compared to patients with a ROS1 rearrangement and wild-type TP53 (7 vs. 24.1 months; p=0.022) (PMID: 30978502; NCT02183870). | 30978502 |
| ROS1 rearrange PIK3CA E545K | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, a patient with non-small cell lung cancer harboring a ROS1 rearrangement demonstrated progression while being treated with Xalkori (crizotinib), and was found to have acquired a PIK3CA E545K mutation (PMID: 30978502; NCT02183870). | 30978502 |
| ROS1 rearrange ROS1 L2026M TP53 P278H | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, a patient with non-small cell lung cancer harboring a ROS1 rearrangement demonstrated progression while being treated with Xalkori (crizotinib), and was found to have acquired two mutations, ROS1 L2026M and TP53 P278H (PMID: 30978502; NCT02183870). | 30978502 |
| ROS1 rearrange ALK neg | lung non-small cell carcinoma | sensitive | Crizotinib | Phase II | Actionable | In a Phase II trial, Xalkori (crizotinib) treatment resulted in an objective response rate of 69% (89/129), and a median duration of treatment of 7.8 months in ALK negative, ROS1 rearranged non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9022); NCT01945021). | detail... |
| ALK rearrange ROS1 rearrange | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in decreased tumor size at 3 months in a patient with lung adenocarcinoma harboring rearrangements in ROS1 and ALK (PMID: 30327151). | 30327151 |
| ALK rearrange ROS1 rearrange | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in decreased tumor size and metabolism in a patient with lung adenocarcinoma harboring rearrangements in ROS1 and ALK (PMID: 28532565). | 28532565 |
| ALK rearrange ROS1 rearrange | lung adenocarcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in lymph node response and progression-free survival greater than 1 year in a patient with EGFR wild-type lung adenocarcinoma harboring rearrangements in ALK and ROS1 (PMID: 29268402). | 29268402 |
| ALK rearrange ROS1 rearrange | lung non-small cell carcinoma | predicted - sensitive | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, Xalkori (crizotinib) treatment resulted in a near complete response and progression-free survival for at least 55 months in a patient with non-small cell lung cancer harboring rearrangements in ALK and ROS1 (PMID: 34459458). | 34459458 |
| Molecular Profile | Protein Effect | Treatment Approaches |
|---|---|---|
| ROS1 rearrange | unknown | ROS1 Inhibitor |
| ROS1 rearrange TP53 mut | ||
| ROS1 rearrange PIK3CA E545K | ||
| ROS1 rearrange ROS1 L2026M TP53 P278H | ||
| ROS1 rearrange ALK neg | ||
| ALK rearrange ROS1 rearrange | ||
| ROS1 rearrange ROS1 G2032R |