Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

Revolution Medicines

Status and phase: Enrolling; Phase 1

Conditions: Non-small Cell Lung Cancer (NSCLC); Colorectal Cancer (CRC); Advanced Solid Tumors; Pancreatic Ductal Adenocarcinoma (PDAC)

Treatments: Drug: RMC-6236

Study type: Interventional

Funder types: Industry

Identifiers

NCT05379985

RMC-6236-001

Details and patient eligibility

About

Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.

Full description

This is a Phase 1/1b, multicenter open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of escalating doses of RMC-6236 in adult patients with advanced solid tumors harboring specific RAS mutations, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose [RP2D] within investigated patient population groups. RMC-6236 is a potent, orally bioavailable RAS-MULTI(ON) inhibitor, selective for the active RAS(ON) form of both wild type and mutant variants of the canonical RAS isoforms (HRAS, NRAS, and KRAS).

Enrollment: 614 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed advanced solid tumor with specific KRAS G12 mutations (dose escalation) or RAS mutations (dose optimization/expansion) identified through deoxyribonucleic acid (DNA) sequencing. PDAC with wild-type RAS (expansion).
• Received prior standard therapy appropriate for tumor type and stage
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function

Exclusion criteria

• Primary central nervous system (CNS) tumors
• Active, untreated brain metastases
• Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
• History of 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

Other inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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614 participants in 1 patient group

Experimental: RMC-6236

Experimental group

Description:

Enrollment into dose exploration may be from any advanced solid tumor type with KRAS p.G12 mutations. Enrollment into dose expansion/optimization may be from groups consisting of patients with a single histotype/genotype (for example, KRAS G12-mutated NSCLC, PDAC, CRC, RAS mutant NSCLC, Melanoma, gynecological cancer or other solid tumors not previously specified). RAS mutant is defined as any nonsynonymous mutation of KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61)

Treatment:

Drug: RMC-6236