Dose-Esc/Exp RMC4630 & Cobi in Relapsed/Refractory Solid Tumors & RMC4630& Osi in EGFR+ Locally Adv/Meta NSCLC

Revolution Medicines

Status and phase

Completed

Phase 2

Phase 1

Conditions

Solid Tumor

Treatments

Drug: Cobimetinib

Drug: Drug: Osimertinib

Drug: RMC-4630

Study type

Interventional

Funder types

Industry

Identifiers

NCT03989115

RMC-4630-02

Details and patient eligibility

About

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.

Full description

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.

Enrollment

113 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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