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

• Status: Active, not recruiting
• Trial end date: 2022-04-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Revolution Medicines, Inc.
• Collaborator: Sanofi
• Treatments: Osimertinib

Criteria

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