Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mutated NSCLC (RASolve 308)

Revolution Medicines

Status and phase: Enrolling; Phase 3

Conditions: Non-Small Cell Lung Cancer NSCLC; Non-small Cell Lung Cancer; Metastatic Non-Squamous Non-Small Cell Lung Cancer; Metastatic NSCLC - Non-Small Cell Lung Cancer; Non-Squamous Non Small Cell Lung Cancer; Lung Cancer (NSCLC); NSCLC

Treatments: Drug: pemetrexed + cisplatin /carboplatin; Drug: zoldonrasib; Drug: pembrolizumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07777822

RMC-9805-308

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 430 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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430 participants in 2 patient groups, including a placebo group

Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet

Experimental group

Description:

study drug in combination with pembrolizumab and platinum-based chemotherapy doublet

Treatment:

Drug: pembrolizumab

Drug: zoldonrasib

Drug: pemetrexed + cisplatin /carboplatin

Arm B: placebo + pembrolizumab + chemotherapy doublet

Placebo Comparator group

Description:

placebo in combination with pembrolizumab and platinum-based chemotherapy doublet

Treatment:

Drug: pembrolizumab

Drug: Placebo

Drug: pemetrexed + cisplatin /carboplatin