Phase 1 RLY-8161 trial tests an NRAS-selective small-molecule inhibitor (NRAS target)

This Phase 1 first-in-human, open-label, multicenter study evaluates RLY-8161—an NRAS-selective small-molecule inhibitor—from Relay Therapeutics in adults with unresectable Stage III/IV NRAS-mutant melanoma or other NRAS-mutant solid tumors. The design includes Part 1 dose escalation (multiple oral dose levels) to define safety/tolerability, pharmacokinetics, pharmacodynamics, and a recommended Phase 2 dose, followed by Part 2 dose expansion at the selected dose(s). The population is molecularly defined (primary oncogenic NRAS mutations, including common Q61 and some G12/G13 variants), which is commercially and scientifically notable because direct NRAS targeting has historically lagged KRAS. In advanced NRAS-mutant melanoma, today’s care is immunotherapy (anti–PD-1 ± anti–CTLA-4), and when immunotherapy fails or isn’t feasible, treatment often shifts to MEK-inhibitor–based approaches or cytotoxic chemotherapy with limited durability—so this trial explores whether direct NRAS inhibition can create a new targeted option. The study is currently listed with 35 planned participants and began in March 2026.