Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mutated NSCLC

A Randomized, Double-blind, Phase 3 Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib (RMC-9805) as First Line Treatment in Patients With Metastatic Non-squamous RAS G12D-Mutated Non-small Cell Lung Cancer (RASolve 308)

The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with pembrolizumab and platinum-based chemotherapy doublet compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet.

This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with pembrolizumab and platinum-based chemotherapy doublet will improve progression-free survival compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet when given to patients with previously untreated, 1L metastatic RAS G12D-mutated, non-squamous non-small cell lung cancer (NSCLC).

Patients will be randomized to one of two arms: zoldonrasib + pembrolizumab + platinum-based chemotherapy doublet (Arm A) or placebo + pembrolizumab + platinum-based chemotherapy doublet (Arm B).

Inclusion Criteria:

• At least 18 years old and has provided informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically or cytologically confirmed, previously untreated metastatic non-squamous NSCLC.
• Known PD-L1 status
• Documented RAS G12D mutation status.
• Measurable disease per RECIST v1.1.
• Adequate organ function (bone marrow, liver, kidney, coagulation, thyroid).
• Able to take oral medications.

Exclusion Criteria:

• Prior treatment with systemic anticancer therapy in metastatic setting for NSCLC.
• Prior systemic therapy with any RAS-directed therapy.
• Untreated (symptomatic or asymptomatic) central nervous system metastatic disease.
• Any conditions that may affect the ability to take or absorb study drug.
• Major surgery on or within 28 days prior to randomization.
• Patient is unable or unwilling to comply with protocol-required study visits or procedures.
• Additional inclusion and exclusion criteria may apply