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| Gene Symbol | ROS1 | ||||||||||
| Synonyms | c-ros-1 | MCF3 | ROS | ||||||||||
| Gene Description | ROS1, ROS proto-oncogene 1, receptor tyrosine kinase, is an orphan receptor tyrosine kinase that may activates multiple pathways involved in cell survival and transformation (PMID: 23719267, PMID: 32327173). ROS1 fusion proteins frequently lead to constitutive activation of Ros1 signaling and have been identified in glioblastoma, non-small cell lung cancer, cholangiocarcinoma, ovarian cancer, gastric adenocarcinoma, colorectal cancer, inflammatory myofibroblastic tumor, angiosarcoma, glioma, and epithelioid hemangioendothelioma (PMID: 23719267, PMID: 30262706, PMID: 30171048, PMID: 3004937), and ROS1 mutations are often associated with acquired resistance to inhibition (PMID: 31256210). | ||||||||||
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ROS1 positive | pancreatic cancer | predicted - sensitive | Entrectinib | Case Reports/Case Series | Actionable | In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in stable disease in a patient with ROS1-positive pancreatic cancer (J Clin Oncol 32:5s, 2014 (suppl; abstr 2502)). | detail... |
| ROS1 positive | 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 (Cancer Res 2019;79(13 Suppl):Abstract nr CT192; NCT02097810; NCT02568267). | detail... detail... |
| ROS1 G2032R | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Biochemical | Actionable | In a preclinical study, Xalkori (crizotinib) treatment did not inhibit kinase activity of a transformed cell line expressing ROS1 G2032R in culture (PMID: 32918045). | 32918045 |
| ROS1 G2032R | Advanced Solid Tumor | predicted - resistant | Ceritinib | Preclinical - Biochemical | Actionable | In a preclinical study, Zykadia (ceritinib) treatment did not inhibit kinase activity of a transformed cell line expressing ROS1 G2032R in culture (PMID: 32918045). | 32918045 |
| ROS1 G2032R | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 G2032R in culture (PMID: 32918045). | 32918045 |
| ROS1 G2032R | Advanced Solid Tumor | predicted - sensitive | SAF-189s | Preclinical - Biochemical | Actionable | In a preclinical study, SAF-189s inhibited kinase activity of a transformed cell line expressing ROS1 G2032R in culture (PMID: 32918045). | 32918045 |
| ROS1 fusion ROS1 G2032R | lung non-small cell carcinoma | predicted - sensitive | Repotrectinib | Phase I | Actionable | In a Phase I/II trial (TRIDENT-1), Augtyro (repotrectinib) treatment resulted in a confirmed objective response rate of 59% (10/17) in patients with TKI-pretreated, ROS1 fusion-positive non-small cell lung cancer harboring ROS1 G2032R (PMID: 38197815; NCT03093116). | 38197815 |
| ROS1 fusion ROS1 G2032R | Advanced Solid Tumor | predicted - sensitive | Repotrectinib | Phase I | Actionable | In a Phase I (TRIDENT-1) trial, Augtyro (repotrectinib) treatment resulted in partial response in a patient with advanced solid tumor harboring ROS1 G2032R in the context of ROS1 fusion (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116). | detail... |
| ROS1 fusion ROS1 G2032R | lung non-small cell carcinoma | predicted - sensitive | Taletrectinib | Case Reports/Case Series | Actionable | In a Phase II trial, Taletrectinib (DS6051b) treatment resulted in a partial response in 3 patients and stable disease in 1 patient out of 4 patients with non-small cell lung cancer harboring ROS1 fusions with secondary ROS1 G2032R mutations ((J Clin Oncol 2022 40:16_suppl, 8572; NCT04395677). | detail... |
| ROS1 fusion ROS1 G2032R | 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 | 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 | 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 | 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 | 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 | 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... |
| 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 | sensitive | 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 | 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 | Advanced Solid Tumor | predicted - sensitive | 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 | 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 2016;76(14 Suppl):Abstract nr CT024; NCT02279433). | detail... |
| ROS1 fusion | lung non-small cell carcinoma | predicted - sensitive | 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 | 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 | 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 | 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 | 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 ROS1 L1951R ROS1 L2026M | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion progressed after 17 months of treatment with Xalkori (crizotinib), and was found to have acquired two additional mutations in trans, ROS1 L2026M and ROS1 L1951R, and cells derived from this patient showed partially decreased SHP2 and ERK1/2 signaling and ROS1 activation (PMID: 29636358). | 29636358 |
| ROS1 fusion ROS1 L1951R ROS1 L2026M | lung non-small cell carcinoma | resistant | Ceritinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient co-harboring a ROS1 fusion, and two other mutations in trans, ROS1 L2026M, and ROS1 L1951R demonstrated resistance to treatment with Zykadia (ceritinib), and cells derived from this patient showed partially decreased SHP2 and ERK1/2 signaling and ROS1 activation (PMID: 29636358). | 29636358 |
| ROS1 fusion KIT D816G | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion developed resistance to treatment with Xalkori (crizotinib) and was subsequently found to have acquired KIT D816G (PMID: 29636358). | 29636358 |
| ROS1 fusion ROS1 S1986F ROS1 L2000V | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with non-small cell lung cancer harboring a ROS1 fusion who had progressed on Xalkori (crizotinib) was subsequently treated with Lorbrena (lorlatinib) but progression ensued and post treatment biopsy revealed acquisition of ROS1 S1986F and ROS1 L2000V (PMID: 33685866). | 33685866 |
| ROS1 L2026M | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 L2026M in culture (PMID: 32918045). | 32918045 |
| ROS1 L2026M | Advanced Solid Tumor | predicted - sensitive | SAF-189s | Preclinical - Biochemical | Actionable | In a preclinical study, SAF-189s inhibited kinase activity of a transformed cell line expressing ROS1 L2026M in culture (PMID: 32918045). | 32918045 |
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 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 | 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 | 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 | 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 | 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 | 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 | 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 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 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 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 | 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 | 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 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 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 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 |
| 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 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 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 |
| ROS1 D2033N | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 D2033N in culture (PMID: 32918045). | 32918045 |
| ROS1 D2033N | Advanced Solid Tumor | predicted - sensitive | SAF-189s | Preclinical - Biochemical | Actionable | In a preclinical study, SAF-189s inhibited the kinase activity of a transformed cell line expressing ROS1 D2033N in culture (PMID: 32918045). | 32918045 |
| ROS1 S1986Y | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 S1986Y in culture (PMID: 32918045). | 32918045 |
| ROS1 S1986Y | Advanced Solid Tumor | predicted - sensitive | SAF-189s | Preclinical - Biochemical | Actionable | In a preclinical study, SAF-189s inhibited kinase activity of a transformed cell line expressing ROS1 S1986Y in culture (PMID: 32918045). | 32918045 |
| ROS1 S1986F | Advanced Solid Tumor | predicted - sensitive | Lorlatinib | Preclinical - Biochemical | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited kinase activity of a transformed cell line expressing ROS1 S1986F in culture (PMID: 32918045). | 32918045 |
| ROS1 S1986F | Advanced Solid Tumor | predicted - sensitive | SAF-189s | Preclinical - Biochemical | Actionable | In a preclinical study, SAF-189s inhibited kinase activity of a transformed cell line expressing ROS1 S1986F in culture (PMID: 32918045). | 32918045 |
| ROS1 D2113G | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited proliferation of transformed cells expressing ROS1 D2113G in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113G | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited proliferation of transformed cells expressing ROS1 D2113G in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113G | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited proliferation of transformed cells expressing ROS1 D2113G in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113G | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) inhibited proliferation of transformed cells expressing ROS1 D2113G in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113G | Advanced Solid Tumor | sensitive | TNO155 | Preclinical - Cell culture | Actionable | In a preclinical study, TNO155 inhibited proliferation of transformed cells expressing ROS1 D2113G in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113G | Advanced Solid Tumor | sensitive | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 inhibited proliferation of transformed cells expressing ROS1 D2113G in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113G | Advanced Solid Tumor | sensitive | NUV-520 | Preclinical - Cell culture | Actionable | In a preclinical study, NUV-520 inhibited proliferation of transformed cells expressing ROS1 D2113G in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113N | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture and inhibited tumor growth and increased survival in a cell line xenograft model (PMID: 37587872). | 37587872 |
| ROS1 D2113N | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture and inhibited tumor growth and increased survival in a cell line xenograft model (PMID: 37587872). | 37587872 |
| ROS1 D2113N | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Koselugo (selumetinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113N | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113N | Advanced Solid Tumor | sensitive | TNO155 | Preclinical - Cell culture | Actionable | In a preclinical study, TNO155 inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113N | Advanced Solid Tumor | sensitive | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
| ROS1 D2113N | Advanced Solid Tumor | sensitive | NUV-520 | Preclinical - Cell culture | Actionable | In a preclinical study, NUV-520 inhibited proliferation of transformed cells expressing ROS1 D2113N in culture (PMID: 37587872). | 37587872 |
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