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| Profile Name | ROS1 fusion |
| Gene Variant Detail | |
| Relevant Treatment Approaches | ROS1 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| 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 | 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 | 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 | Advanced Solid Tumor | predicted - sensitive | Entrectinib | Clinical Study | Actionable | In a combined analysis of 2 Phase I trials (ALKA-372-001, STARTRK-1), Rozlytrek (entrectinib) treatment resulted 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; NCT02097810). | 28183697 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Entrectinib | Clinical Study | Actionable | In a combined analysis of 2 Phase I trials (ALKA-372-001, STARTRK-1), Rozlytrek (entrectinib) treatment resulted in a 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; NCT02097810). | 28183697 |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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: 30285222; ESMO.org). | detail... 30285222 |
| 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: 30285222; ESMO.org). | 30285222 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 | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as a first-line or subsequent 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 | 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 | 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 | 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 | 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 | 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: 30285222, Version Update 15 Sept 2020; ESMO.org). | 30285222 detail... |
| 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: 30285222, Version Update 15 Sept 2020; ESMO.org). | 30285222 detail... |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) 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: 30285222, Version Update 15 Sept 2020; ESMO.org). | detail... 30285222 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Iruplinalkib | Phase I | Actionable | In a Phase I trial, Iruplinalkib (WX-0593) 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 | 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 | Cancer of Unknown Primary | sensitive | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines for patients with cancer of unknown primary harboring ROS1 rearrangements (PMID: 36563965, PMID: 30285222; ESMO.org). | detail... 30285222 36563965 |
| ROS1 rearrange | lung non-small cell carcinoma | predicted - sensitive | Carboplatin + Pembrolizumab + Pemetrexed Disodium | Clinical Study - Cohort | Actionable | In a retrospective analysis, immune checkpoint inhibitor plus chemotherapy (including Keytruda (pembrolizumab) plus pemetrexed and carboplatin, n=11) in ROS1-rearranged non-small cell lung cancer patients led to an overall response rate (ORR) of 83% (5/6), disease control rate (DCR) of 100%, and duration of response (DOR) of 24.3 mo as first-line, an ORR of 28.6% (4/14), DCR of 92.9%, and DOR of 4.8 mo as subsequent-line, and an intracranial ORR of 40% (4/10) and intracranial DCR of 90% (PMID: 36952645). | 36952645 |
| ROS1 rearrange | lung non-small cell carcinoma | predicted - sensitive | Carboplatin + Paclitaxel + Pembrolizumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, immune checkpoint inhibitor plus chemotherapy (including Keytruda (pembrolizumab) plus paclitaxel and carboplatin, n=7) in ROS1-rearranged non-small cell lung cancer patients led to an overall response rate (ORR) of 83% (5/6), disease control rate (DCR) of 100%, and duration of response (DOR) of 24.3 mo as first-line, an ORR of 28.6% (4/14), DCR of 92.9%, and DOR of 4.8 mo as subsequent-line, and an intracranial ORR of 40% (4/10) and intracranial DCR of 90% (PMID: 36952645). | 36952645 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | TQ-B3101 | Phase Ib/II | Actionable | In a Phase I/II trial, TQ-B3101 treatment demonstrated safety and resulted in an objective response rate (ORR) of 80.2% (89/111, 1 complete response (CR), 88 partial (PR)), disease control rate (DCR) of 88.3%, median duration of response of 20.3 mo, median progression-free survival of 16.5 mo, and intracranial ORR of 72.7% (8/11, 1 CR, 7 PR) and DCR of 90.9% in patients with non-small cell lung cancer harboring ROS1 rearrangements (PMID: 37385995; NCT03019276, NCT03972189). | 37385995 |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Repotrectinib | Guideline | Actionable | Augtyro (repotrectinib) is included in guidelines as first-line or subsequent therapy for patients with advanced or metastatic non-small cell lung cancer harboring a ROS1 rearrangement (NCCN.org). | detail... |
| ROS1 rearrange | lung non-small cell carcinoma | sensitive | Foritinib | Phase II | Actionable | In a Phase II trial, Foritinib treatment led to an 89% (65/73, 65 partial responses (PR)) objective response rate (ORR), median duration of response (mDOR) of 20.7 mo, and median progression-free survival (mPFS) of 22.1 mo in ROS1 inhibitor-naive non-small cell lung cancer patients harboring a ROS1 rearrangement, including a 92.3% (24/26) ORR in patients with CNS lesions, and a 40% (10/25, 10 PR) ORR, mDOR of 7.0 mo, and mPFS of 5.5 mo in patients who received prior crizotinib (PMID: 39059398; NCT04237805). | 39059398 |