The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

This is an open-label, multicenter, Phase 1/1b study of RMC-6291 monotherapy in subjects with advanced KRASG12C-mutant solid tumors. The study will include 2 components: a Dose-Escalation and a Dose-Expansion. Subjects will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Inclusion Criteria:

• Subject must be ≥18 years of age.
• Subject must have pathologically documented, locally advanced or metastatic KRASG12C-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments.
• ECOG performance status 0 or 1
• Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation and for NSCLC in dose expansion
• Adequate organ function

Exclusion Criteria:

• Primary central nervous system (CNS) tumors
• Active brain metastases
• Known impairment of GI function that would alter the absorption
• Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.
• Prior therapy with KRASG12C (ON) inhibitor

Other inclusion/exclusion criteria may apply.