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| Profile Name | ROS1 fusion |
| Gene Variant Detail | |
| Relevant Treatment Approaches | ROS1 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| ROS1 fusion | lung non-small cell carcinoma | sensitive | ROS1 Inhibitor | 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 | sensitive | ROS1 Inhibitor | 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 | predicted - sensitive | ROS1 Inhibitor | Taletrectinib | Phase I | Actionable | In a Phase I trial, Taletrectinib (DS6051b) 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 2016;76(14 Suppl):Abstract nr CT024; NCT02279433). | detail... |
| ROS1 fusion | Advanced Solid Tumor | predicted - sensitive | ROS1 Inhibitor | Repotrectinib | Phase I | Actionable | In a Phase I (TRIDENT-1) trial, Augtyro (repotrectinib) 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 | sensitive | ROS1 Inhibitor | 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 | ROS1 Inhibitor | Entrectinib | FDA approved - On Companion Diagnostic | 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 | lung non-small cell carcinoma | sensitive | ROS1 Inhibitor | 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 | 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 | Advanced Solid Tumor | predicted - sensitive | ROS1 Inhibitor | 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 | predicted - sensitive | ROS1 Inhibitor | Taletrectinib | Phase II | Actionable | In a Phase II trial (TRUST-I), Taletrectinib (DS6051b) treatment in non-small cell lung cancer patients with ROS1 fusions resulted in a 90.6% (96/106) overall response rate (ORR) and 95.3% disease control rate (DCR) in TKI-naive patients and 51.5% (34/66) ORR and 83.3% DCR in crizotinib-pretreated patients, intracranial ORR of 87.5% (7/8) and DCR of 100% in patients with baseline brain lesions, and partial responses in 8 of 12 patients with secondary ROS1 G2032R mutations (PMID: 38822758; NCT04395677). | 38822758 |
| ROS1 fusion | lung non-small cell carcinoma | predicted - sensitive | ROS1 Inhibitor | NUV-520 | Phase I | Actionable | In a Phase I trial (ARROS-1), NUV-520 treatment demonstrated safety and activity in patients with non-small cell lung cancer harboring a ROS1 fusion, resulting in a response rate of 38% (28/73), including a complete response in 2 patients with a duration of response of at least 16.6 mo and 23.5 mo, and median DOR was not reached (Ann Oncol (2024) 35 (Suppl_2): S804-S805; NCT05118789). | detail... |
| ROS1 fusion | skin melanoma | sensitive | ROS1 Inhibitor | Crizotinib | Guideline | Actionable | Xalkori (crizotinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with ROS1 fusions (NCCN.org). | detail... |
| ROS1 fusion | skin melanoma | sensitive | ROS1 Inhibitor | Entrectinib | Guideline | Actionable | Rozlytrek (entrectinib) is included in guidelines as second-line therapy for metastatic or unresectable cutaneous melanoma patients with ROS1 fusions (NCCN.org). | detail... |
| ROS1 fusion | lung non-small cell carcinoma | sensitive | ROS1 Inhibitor | Repotrectinib | Phase Ib/II | Actionable | In a Phase I/II trial (TRIDENT-1), Augtyro (repotrectinib) treatment resulted in an intracranial objective response rate (icORR) of 88% (7/8) with intracranial duration of response (DOR) ranging from 1.9-14.8 months in non-small cell lung cancer patients harboring ROS1 fusions who were TKI-naive, and an icORR of 42% (5/12) with intracranial DOR ranging from 3.0-11.1 months in those with 1 prior TKI and no chemo (J Clin Oncol 41, 2023 (suppl 16; abstr 9017); NCT03093116). | detail... |
| ROS1 fusion | lung non-small cell carcinoma | predicted - sensitive | TQ-B3139 | Case Reports/Case Series | Actionable | In a Phase I trial, TQ-B3139 (CT-711) treatment demonstrated safety and resulted in an overall response rate (ORR) of 61.9% (39/63), intracranial ORR of 70% (7/10), disease control rate of 84.1% (53/63), and median progression-free survival (mPFS) of 19.0 mo in non-small cell lung cancer patients harboring an ALK or ROS1 fusion, with longer mPFS in TKI-naive patients (25.2 mo vs 5.4 mo), and an ORR of 66.7% (2/3), including 1 complete response, in patients with ROS1 fusions (PMID: 35940055; NCT03099330). | 35940055 | |
| ROS1 fusion | lung non-small cell carcinoma | predicted - sensitive | ROS1 Inhibitor | Taletrectinib | Phase II | Actionable | In a Phase II trial (TRUST-II), Taletrectinib (DS6051b) treatment demonstrated safety in ROS1 fusion-positive non-small cell lung cancer patients and resulted in a confirmed investigator-assessed objective response rate (cORRinv) of 94% (17/18) and a disease control rate (DCR) of 100% in the treatment-naive cohort and a cORRinv of 55% (12/22) and DCR of 91% in the previously treated cohort (Ann Oncol (2023) 34 (suppl_2):S788-S789; NCT04919811). | detail... |
| ROS1 fusion | lung non-small cell carcinoma | sensitive | ROS1 Inhibitor | Repotrectinib | FDA approved | Actionable | In a Phase I/II trial (TRIDENT-1) that supported FDA approval, Augtyro (repotrectinib) resulted in an objective response rate of 79% (56/71, 7 complete and 49 partial responses) and 38% (21/56, 3 complete and 18 partial responses), median duration of response of 34.1 and 14.8 months, and a median progression-free survival of 35.7 and 9.0 months in patients with TKI-naive and TKI-treated, ROS1 fusion-positive non-small cell lung cancer, respectively (PMID: 38197815; NCT03093116). | 38197815 detail... |
| ROS1 fusion | lung non-small cell carcinoma | sensitive | ROS1 Inhibitor | Entrectinib | Phase II | Actionable | In a Phase II/III trial (BFAST), Rozlytrek (entrectinib) treatment demonstrated safety and efficacy in treatment-naive advanced non-small cell lung cancer patients with ROS1 fusions detected by liquid biopsy, resulting in an investigator-assessed objective response rate of 81.5% (44/54, 2 complete and 42 partial responses), clinical benefit rate of 87% (47/54), stable disease in 7 patients, median duration of response of 13 mo, and median progression-free survival of 12.9 mo (PMID: 38898120; NCT03178552). | 38898120 |
| ROS1 fusion | Advanced Solid Tumor | predicted - sensitive | ROS1 Inhibitor | Entrectinib | Clinical Study - Cohort | Actionable | In a combined analysis of 3 clinical trials (STARTRK-NG, TAPISTRY, STARTRK-2), Rozlytrek (entrectinib) treatment resulted in an objective response rate (ORR) of 65.0% (13/20, 3 complete (CR) and 10 partial (PR) responses) in pediatric patients (median age 7.5 yo) with solid tumors harboring ROS1 fusions, with median time to response of 1.87 mo, ORR was 58.3% (7/12, 1 CR, 6PR) in patients with extracranial solid tumors (PMID: 40086048; NCT02650401, NCT04589845, NCT02568267). | 40086048 |
| ROS1 fusion | central nervous system cancer | predicted - sensitive | ROS1 Inhibitor | Entrectinib | Clinical Study - Cohort | Actionable | In a combined analysis of 3 clinical trials (STARTRK-NG, TAPISTRY, STARTRK-2), Rozlytrek (entrectinib) treatment resulted in an objective response rate (ORR) of 65.0% (13/20, 3 complete (CR) and 10 partial (PR) responses) in pediatric patients (median age 7.5 yo) with solid tumors harboring ROS1 fusions, with median time to response of 1.87 mo, ORR was 75.0% (6/8, 2 CR, 4 PR) in patients with CNS tumors (PMID: 40086048; NCT02650401, NCT04589845, NCT02568267). | 40086048 |