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
- 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 .
- 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
Revolution Medicines, Inc.
- Primary ID RMC-4630-02
- Secondary IDs NCI-2019-04826
- Clinicaltrials.gov ID NCT03989115