A First-in-human Study of RLY-8161 in Advanced NRAS-Mutant Solid Tumors

This is a Phase 1/2 first-in-human, open-label multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of RLY-8161, an NRAS-selective inhibitor, in participants with advanced NRAS-mutant melanoma, colorectal and other solid tumors.

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Histologically confirmed diagnosis of unresectable Stage III or IV melanoma or other solid tumor. * Disease is refractory to standard therapy (including targeted therapy), participant is intolerant of standard therapy, or participant has declined standard therapy. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * One or more documented primary oncogenic NRAS mutation(s). Exclusion Criteria: * Known activating KRAS, HRAS, BRAF, or EGFR mutation or known alterations in other driver oncogenes that are recognized as actionable oncogenic drivers for the participant's specific tumor type. * Prior treatment with ERK, MEK, RAF, or RAS targeting agents or any agent whose mechanism of action is to inhibit the RAS-MAPK pathway. * For participants with melanoma: lactate dehydrogenase (LDH) \>2×ULN. * Central nervous system (CNS) metastases associated with progressive neurologic symptoms or requiring ongoing corticosteroids to control the CNS disease.