Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Profile Name | NRAS act mut |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
NRAS act mut | lung non-small cell carcinoma | predicted - resistant | Osimertinib | Case Reports/Case Series | Actionable | In a retrospective analysis, activating NRAS mutations were identified in 1 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). | 31839416 | |
NRAS act mut | Advanced Solid Tumor | no benefit | Selumetinib | Clinical Study - Cohort | Actionable | In a Phase II trial (MATCH), Koselugo (selumetinib) treatment resulted in a 15% (3/20) six-month progression-free survival rate, no objective responses, and did not lead to tumor regression in pediatric patients with advanced solid tumors including high grade glioma (n=8) and rhabdomyosarcoma (n=7) that harbored MAPK pathway alterations including activating NRAS, HRAS, or KRAS mutations, BRAF V600E, or inactivating NF1 mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 10008; NCT03213691, NCT03155620). | detail... | |
NRAS act mut | melanoma | predicted - sensitive | Binimetinib + KIN-2787 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, KIN-2787 and Mektovi (binimetinib) combination treatment inhibited growth of melanoma cell lines harboring NRAS mutations in culture, and resulted in improved tumor growth inhibition and Mapk pathway suppression in cell line xenograft models compared to either agent alone (J Clin Oncol 40, 2022 (suppl 16; abstr e15099)). | detail... | |
NRAS act mut | melanoma | predicted - sensitive | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib/II trial, Kisqali (ribociclib) plus Mektovi (binimetinib) was well tolerated in NRAS-mutant melanoma patients and resulted in an overall response rate of 19.5% (8/41; all PR), disease control rate of 70.7% (29/41), median duration of response of 10.3mo, median progression-free survival of 3.7mo, and median overall survival of 11.3mo in phase II, and a response rate of 22.9% (16/70) in patients with an NRAS Q61 mutation, and 12.5% (1/8) with NRAS G12/G13 mutation (PMID: 35294522; NCT01781572). | 35294522 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT03114319 | Phase I | TNO155 | Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors | Recruiting | USA | ESP | CAN | 5 |
NCT04418167 | Phase I | JSI-1187 Dabrafenib + JSI-1187 | JSI-1187-01 Monotherapy and in Combination With Dabrafenib for Advanced Solid Tumors With MAPK Pathway Mutations | Recruiting | USA | 0 |
NCT04249843 | Phase I | BGB3245 | Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors | Recruiting | USA | 1 |
NCT04487106 | Phase II | Azacitidine + Trametinib + Venetoclax | Azacitidine, Venetoclax, and Trametinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndrome | Recruiting | USA | 0 |
NCT05340621 | Phase Ib/II | Binimetinib + OKI-179 | OKI-179 Plus Binimetinib in Patients With Advanced Solid Tumors in the RAS Pathway (Phase 1b) and NRAS-mutated Melanoma (Phase 2) | Recruiting | USA | 0 |
NCT03919071 | Phase II | Dabrafenib + Trametinib | Dabrafenib Combined With Trametinib After Radiation Therapy in Treating Patients With Newly-Diagnosed High-Grade Glioma | Recruiting | USA | 1 |
NCT03429803 | Phase I | MLN2480 | DAY101 In Gliomas and Other Tumors | Active, not recruiting | USA | 0 |
NCT02097225 | Phase I | Dabrafenib + Onalespib + Trametinib | Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery | Active, not recruiting | USA | 0 |
NCT03973918 | Phase II | Binimetinib + Encorafenib | Study of Binimetinib With Encorafenib in Adults With Recurrent BRAF V600-Mutated HGG (BRAF) | Active, not recruiting | USA | 0 |
NCT02587650 | Phase II | Ceritinib Capmatinib Regorafenib Entrectinib | Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma | Terminated | USA | 0 |
NCT03979651 | Phase Ib/II | Hydroxychloroquine + Trametinib | MEK and Autophagy Inhibition in Metastatic/Locally Advanced, Unresectable Neuroblastoma RAS (NRAS) Melanoma (CHLOROTRAMMEL) | Unknown status | FRA | 0 |
NCT04587128 | Phase II | Cetuximab Cetuximab + Irinotecan Panitumumab Irinotecan + Panitumumab | Early-Line Anti-EGFR Therapy to Facilitate Retreatment for Select Patients With mCRC | Recruiting | USA | 0 |
NCT02257424 | Phase Ib/II | Dabrafenib + Hydroxychloroquine + Trametinib | Dabrafenib, Trametinib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma (BAMM) | Completed | USA | 0 |
NCT05111561 | Phase I | Binimetinib + ZEN-3694 | Testing the Combination of the Anticancer Drugs ZEN003694 and Binimetinib in Patients With Advanced/Metastatic or Unresectable Solid Tumors With RAS Alterations and Triple Negative Breast Cancer | Recruiting | USA | 0 |
NCT02974803 | Phase II | Dabrafenib + Trametinib | Concurrent Dabrafenib + Trametinib With Sterotactic Radiation in BRAF Mutation-Positive Malignant Melanoma and Brain Metastases | Terminated | CAN | 0 |
NCT04699188 | Phase Ib/II | JDQ443 JDQ443 + TNO155 JDQ443 + Spartalizumab JDQ443 + Spartalizumab + TNO155 | Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation | Recruiting | USA | ITA | FRA | ESP | DEU | CAN | BEL | 9 |
NCT03310541 | Phase I | Capivasertib Capivasertib + Enzalutamide Capivasertib + Fulvestrant | AZD5363 in Patients With Advanced Solid Tumors Harboring AKT Mutations | Active, not recruiting | USA | 0 |