Yan Leyfman, Medical Oncologist, Co-Founder and Executive Director of MedNews Week, shared a post on LinkedIn about a paper by Keiran S.M. Smalley et al. published in Cancer Immunology Research:
“Breakthrough in NRAS-mutant melanoma!
Targeted therapies for NRAS-mutant melanoma have long been an unmet clinical need. In this study, researchers highlight RMC-7977, a preclinical RAS(ON) multi-selective inhibitor (representative of daraxonrasib, RMC-6236), which triggered potent antitumor immune responses across multiple NRAS-mutant melanoma models.
Key findings:
- Induced rapid tumor regressions via MAPK inhibition and upregulation of MHC and PD-L1
- Enhanced CD4⁺ and CD8⁺ T-cell infiltration — essential for long-term survival
- Resistance linked to reduced T-cell infiltration and loss of MHC class I
- Combining RMC-7977 with anti–PD-1 therapy boosted T-cell infiltration, reprogrammed myeloid cells, and improved survival—even in PD-1–resistant models
Notably, two NRAS-mutant melanoma patients treated with daraxonrasib in an ongoing Phase I/Ib trial achieved objective clinical responses.
These results underscore the promise of RAS(ON) multi-selective inhibitors as a novel therapeutic strategy for NRAS-mutant melanoma.”
Title: RAS(ON) multi-selective inhibition drives antitumor immunity in preclinical models of NRAS-mutant melanoma
Authors: Larissa Anastacio Da Costa Carvalho, Nataliya Tovbis Shifrin, Manali S. Phadke, Michael F. Emmons, Ximo Pechuan-Jorge, Felix Mbuga, Oscar E. Ospina, Christopher Chow, Lillian Seu, Olivia L. Rose, Aparna Hegde, Nikhil I. Khushalani, Elsa Quintana, Keiran S.M. Smalley
You can read the full article in Cancer Immunology Research.
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