Molecular Profile Detail

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Profile Name NRAS act mut
Gene Variant Detail

NRAS act mut (unknown)

Relevant Treatment Approaches

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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 (Pediatric MATCH), Koselugo (selumetinib) treatment was tolerated but did not result in an objective response in pediatric patients with advanced solid tumors including high-grade glioma (n=8) and rhabdomyosarcoma (n=7) harboring MAPK pathway alterations including BRAF V600E (n=2), activating KRAS (n=8)/HRAS (n=1)/NRAS (n=3) or inactivating NF1 (n=7) mutations, with a 6-month progression-free survival of 15% (3/20) and 3 stable disease as best response (PMID: 35363510; NCT03213691). 35363510
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
NRAS act mut melanoma predicted - sensitive Binimetinib + Exarafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Exarafenib (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 FCN-159 Phase I Actionable In a Phase I trial (FCN-159-001), FCN-159 treatment was well tolerated in melanoma patients harboring NRAS activating mutations and resulted in an objective response rate (ORR) of 19% (4/21, all partial responses), a clinical benefit rate (CBR) of 52.4% (11/21), and a median progression-free survival (mPFS) of 3.8 mo across all doses tested, and a CBR of 50% (3/6), mPFS of 3.8 mo at the RP2D dose of 12mg (PMID: 36113242; NCT03932253). 36113242
NRAS act mut multiple myeloma predicted - sensitive BMF-219 Preclinical - Cell culture Actionable In a preclinical study, BMF-219 inhibited growth of multiple myeloma cell lines harboring NRAS activating mutations in culture (Cancer Res 2022;82(12_Suppl):Abstract nr 2654). detail...
NRAS act mut melanoma predicted - sensitive Tunlametinib Phase I Actionable In a Phase I trial, Tunlametinib (HL-085) treatment demonstrated acceptable tolerability and resulted in an objective response rate (ORR) of 14.3% (6/42; all partial responses), a disease control rate (DCR) of 78.6%, and a median progression-free survival (PFS) of 3.0 months in patients with advanced melanoma harboring NRAS mutations, and an ORR of 26.7% (4/15), a DCR of 86.7%, and median PFS of 3.6 months at the recommended Phase II dose (PMID: 36600247; NCT03973151). 36600247
NRAS act mut neuroblastoma predicted - sensitive Navitoclax + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an NRAS activating mutation to Navitoclax (ABT-263), resulting in reduced cell viability in culture, and the combination treatment resulted in tumor regression in cell line xenograft models (6/6 partial responses) (PMID: 36895472). 36895472
NRAS act mut neuroblastoma predicted - sensitive Trametinib + Venetoclax Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an NRAS activating mutation to Venclexta (venetoclax), resulting in reduced cell viability in culture, and the combination treatment resulted in tumor growth inhibition with 2/6 partial responses and 3/6 with stable disease in cell line xenograft models (PMID: 36895472). 36895472
NRAS act mut neuroblastoma predicted - sensitive S63845 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an NRAS activating mutation to S63845 (MIK655), resulting in reduced cell viability in culture (PMID: 36895472). 36895472
NRAS act mut melanoma predicted - sensitive Exarafenib Case Reports/Case Series Actionable In a Phase I trial, Exarafenib (KIN-2787) was tolerated and resulted in a partial response in 17.6% (6/34) and stable disease in 23.5% (8/34) of patients with BRAF-driven advanced solid tumors or NRAS-driven melanoma, including a partial response in 1 melanoma patient harboring an NRAS mutation (Cancer Res (2023) 83 (8_Supplement): CT032; NCT04913285). detail...
NRAS act mut melanoma decreased response Toripalimab-tpzi Clinical Study Actionable In a retrospective analysis, real-world treatment with either Keytruda (pembrolizumab) or Loqtorz (toripalimab-tpzi) resulted in a median disease-free survival of 9 months in melanoma patients harboring activating NRAS mutations in either G12 (29%) or Q61 (67.1%) compared to 32 months in patients with wild-type BRAF, NRAS, and KIT (p<0.0001) (PMID: 37403699). 37403699
NRAS act mut melanoma decreased response Pembrolizumab Clinical Study Actionable In a retrospective analysis, real-world treatment with either Keytruda (pembrolizumab) or Toripalimab (JS001) resulted in a median disease-free survival of 9 months in melanoma patients harboring activating NRAS mutations in either G12 (29%) or Q61 (67.1%) compared to 32 months in patients with wild-type BRAF, NRAS, and KIT (p<0.0001) (PMID: 37403699). 37403699
NRAS act mut melanoma predicted - sensitive Tunlametinib Phase II Actionable In a Phase II trial, Tunlametinib (HL-085) treatment demonstrated safety and activity in Chinese patients with advanced melanoma harboring NRAS mutations (including mutations at Q61, G12, and G13), with an objective response rate of 35.8% (34/95, all partial responses), a median progression-free survival of 4.2 months, disease control rate of 72.6% (69/95), median duration of response of 6.1 months, and median overall survival of 13.7 months (PMID: 38479118; NCT05217303). 38479118