Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

Phase 1

Active, not recruiting

• Conditions: Advanced Solid Tumor; Non-Small Cell Lung Cancer (NSCLC); Colorectal Cancer (CRC); Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: RMC-6291

• Registration Number: NCT05462717
• Lead Sponsor: Revolution Medicines, Inc.

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

Detailed Description

This is an open-label, multicenter, Phase 1/1b study of RMC-6291 monotherapy in subjects with advanced KRASG12C-mutant solid tumors. The study will include 2 components: a Dose-Escalation and a Dose-Expansion. Subjects will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Study Timeline

• Study First Submitted: 2022-07-11
• Study First Submitted QC: 2022-07-13
• Study First Posted: 2022-07-18
• Study Start: 2022-09-19
• Status Verified: 2024-06
• Primary Completion: 2024-11
• Last Update Submitted: 2024-11-05
• Last Update Posted: 2024-11-07
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 222

Inclusion Criteria

• Subject must be ≥18 years of age.
• Subject must have pathologically documented, locally advanced or metastatic KRASG12C-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments.
• ECOG performance status 0 or 1
• Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation
• Adequate organ function

Exclusion Criteria

• Primary central nervous system (CNS) tumors
• Active brain metastases
• Known impairment of GI function that would alter the absorption
• Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.
• Prior therapy with KRASG12C (ON) inhibitor

Other inclusion/exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RMC-6291	RMC-6291	Dose Escalation and Dose Expansion

Primary Outcome Measures

Name	Time	Method
Adverse events	up to 3 years	Number of participants with adverse events
Dose Limiting Toxicities	The first 21 days (i.e. Cycle 1)	Number of participants with dose limiting toxicities

Secondary Outcome Measures

Name	Time	Method
Maximum Observed Blood Concentration of RMC-6291	7 Cycles	Cmax
Time to Reach Maximum Blood Concentration of RMC-6291	7 Cycles	Tmax
Area Under Blood Concentration Time Curve of RMC-6291	7 Cycles	AUC
Elimination Half-Life of RMC-6291	7 Cycles	t1/2
Overall Response Rate (ORR)	3 years	Overall response rate per RECIST v1.1
Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing	7 Cycles	accumulation ratio
Time to Response (TTR)	3 years	Time to response per RECIST v1.1
Progression-Free Survival (PFS)	3 years	Progression-free survival per RECIST v1.1
Duration of Response (DOR)	3 years	Duration of response per RECIST v1.1
Disease Control Rate (DCR)	3 years	Disease control rate per RECIST v1.1

Trial Locations

Locations (64)

Highlands Oncology Group; 🇺🇸 Springdale, Arkansas, United States

UC Irvine Cancer Center; 🇺🇸 Orange, California, United States

UC Davis Cancer Center; 🇺🇸 Sacramento, California, United States

UCSF; 🇺🇸 San Francisco, California, United States

University of Miami School of Medicine Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

American Oncology Partners of Maryland; 🇺🇸 Bethesda, Maryland, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

MSK Cancer Center; 🇺🇸 New York, New York, United States

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