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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

Trial Status: Active

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

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: ACTIVE
Contact: Thanh Phan
Phone: 714-456-5723
Email: tphan@uci.edu
Sacramento
University of California Davis Comprehensive Cancer Center
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Status: ACTIVE
Contact: Helen Diller Family Comprehensive Cancer Center
Phone: 877-827-3222

Colorado

Denver
University of Colorado
Status: ACTIVE

Florida

Tampa
Moffitt Cancer Center
Status: ACTIVE

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE

Illinois

Chicago
Northwestern University
Status: ACTIVE

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: WITHDRAWN
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Kathryn C Arbour
Phone: 646-449-1775

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: ACTIVE
Contact: systems coordinator
Phone: 215-214-1558

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: ACTIVE

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