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|Gene Variant Descriptions||ROS1 fusion indicates a fusion of the ROS1 gene, but the fusion partner is unknown.|
|Associated Drug Resistance|
|Category Variants Paths||
ROS1 mutant ROS1 rearrange ROS1 fusion
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|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||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||predicted - sensitive||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 July 15 2016 (76) (14 Supplement) CT024).||detail...|
|ROS1 fusion||lung non-small cell carcinoma||predicted - sensitive||Taletrectinib||Phase II||Actionable||In a Phase II trial, Taletrectinib (DS6051b) treatment in non-small cell lung cancer patients with ROS1 fusions resulted in a 90% (36/40) overall response rate (ORR) and 95% disease control rate (DCR) in TKI-naive patients and 47.6% (10/21) ORR and 76.2% DCR in crizotinib-pretreated patients, intracranial ORR of 83.3% (5/6) and DCR of 100% in patients with baseline brain lesions, and partial responses in 3 of 4 patients with secondary ROS1 G2032R mutations (J Clin Oncol 2022 40:16_suppl, 8572; NCT04395677).||detail...|
|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||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||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||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||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||NUV-520||Phase I||Actionable||In a Phase I trial (ARROS-1), NUV-520 treatment resulted in 6 partial responses among 12 patients with non-small cell lung cancer harboring a ROS1 fusion including a partial response in 5 of 7 patients harboring a ROS1 fusion with ROS1 G2032R (Eu J Cancer 2022 Vol 174, Supp 1:S6-S7; NCT05118789).||detail...|
|ROS1 fusion||skin melanoma||sensitive||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||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...|