Dose-Escalation / Expansion of RMC-4630 and Cobimetinib in Relapsed / Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced / Metastatic NSCLC

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and cobimetinib in adult participants with relapsed / refractory solid tumors with specific genomic aberrations and to identify the recommended Phase 2 dose (RP2D); and to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of RMC-4630 and osimertinib in adult participants with EGFR mutation-positive locally advanced or metastatic NSCLC.

Inclusion Criteria

• Age ≥18 years
• For RMC-4630 + Cobimetinib only - Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anti-cancer treatments including approved drugs for oncogenic drivers in their tumor type.
• For RMC-4630 + Osimertinib only - Locally advanced or metastatic EGFR mutant NSCLC not amenable to curative surgery or radiotherapy
• For RMC-4630 + Cobimetinib only - Participants must have one of the following genotypic aberrations: KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations
• For RMC-4630 + Osimertinib only - Evidence of radiological documentation of progression with osimertinib monotherapy or an osimertinib containing regimen. Participants should not be considered a current candidate for 1st generation EGFR TKI's by the investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Adequate hematological, hepatic, and renal function
• Capable of giving signed informed consent form (ICF). Willing and able to compile with study requirements and restrictions
• Life expectancy >12 weeks
• Female of childbearing potential and males with partners of childbearing potential must comply with effective contraception criteria .

Exclusion Criteria

• Primary central nervous system (CNS) tumors.
• Known or suspected leptomeningeal or brain metastases or spinal cord compression.
• For RMC-4630 + osimertinib arm only - Known or suspected Small cell, squamous, or pleomorphic lung transformations
• Clinically significant cardiac disease
• Active, clinically significant interstitial lung disease or pneumonitis
• History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
• Known HIV infection or active/chronic hepatitis B or C infection.
• Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
• Females who are pregnant or breastfeeding

This open-label, phase 1b/2 dose-escalation and dose-expansion study is designed to evaluate

the safety and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of RMC-4630

in combination with cobimetinib in participants with relapsed/refractory solid tumors; and of

RMC-4630 in combination with osimertinib in adult participants with EGFR mutation-positive

locally advanced or metastatic NSCLC.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Revolution Medicines, Inc.

• Primary ID RMC-4630-02
• Secondary IDs NCI-2019-04826
• Clinicaltrials.gov ID NCT03989115