Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies

Phase 2

Completed

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: RMC-4630; Drug: Sotorasib

• Registration Number: NCT05054725
• Lead Sponsor: Revolution Medicines, Inc.

Brief Summary

The purpose of this study is to evaluate the antitumor effects of sotorasib and RMC-4630 in subjects with KRASG12C mutant NSCLC

Detailed Description

This is a phase 2 multicenter, open-label study evaluating the efficacy, safety, tolerability, and pharmacokinetics (PK) of RMC-4630 in combination with sotorasib in subjects with KRASG12C mutant NSCLC after failure of prior standard therapies.

Study Timeline

• Study First Submitted: 2021-09-14
• Study First Submitted QC: 2021-09-14
• Study First Posted: 2021-09-23
• Study Start: 2021-12-30
• Primary Completion: 2024-07-03
• Study Completion: 2024-08-29
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

• Subject must be ≥18 years of age.
• Subject must have pathologically documented, locally advanced or metastatic KRASG12C NSCLC (not amenable to curative surgery) that has progressed on prior standard therapies (no more than 3 prior lines of therapies are allowed)

Exclusion Criteria

• Primary central nervous system (CNS) tumors
• Known or suspected leptomeningeal or brain metastases or spinal cord compression
• Clinically significant cardiac disease
• Known impairment of GI function that would alter the absorption
• Active autoimmune disease requiring systemic treatment within past 2 years
• History of severe allergic reactions to any of the study intervention components
• Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.
• Prior therapy with KRASG12C inhibitor and/or SHP2 inhibitor

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
RMC-4630 and sotorasib, Safety Run-in	RMC-4630	Safety Run-In: RMC-4630 and sotorasib
RMC-4630 and sotorasib, Safety Run-in	Sotorasib	Safety Run-In: RMC-4630 and sotorasib
RMC-4630 and sotorasib, Expansion	RMC-4630	Dose Expansion: RMC-4630 and sotorasib
RMC-4630 and sotorasib, Expansion	Sotorasib	Dose Expansion: RMC-4630 and sotorasib

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	approximately 12 months	ORR as assessed per RECIST v1.1

Secondary Outcome Measures

Name	Time	Method
Vital signs	approximately 12 months	Number of subjects with clinically significant changes in vital signs
ECGs Measurements	approximately 12 months	Number of subjects with clinically significant changes in ECGs Measurements
Concentration of sotorasib	approximately 12 months	Trough Concentration of sotorasib
Overall survival (OS)	approximately 12 months	Overall survival (OS)
Clinical laboratory test values	approximately 12 months	Number of subjects with clinically significant changes in clinical laboratory test values
Duration of response (DOR)	approximately 12 months	DOR as assessed by RECIST v1.1
Adverse Events	approximately 12 months	Number of Participants with Adverse Events
Concentration of RMC-4630	approximately 12 months	Trough Concentration of RMC-4630
Progression-free survival (PFS)	approximately 12 months	PFS as assessed by RECIST v1.1
Disease Control Rate (DCR)	approximately 12 months	DCR as assessed by RECIST v1.1
Serious Adverse Events	approximately 12 months	Number of Participants with Serious Adverse Events

Trial Locations

Locations (59)

Florida Cancer Specialists; 🇺🇸 Fort Myers, Florida, United States

BRCR Medical Center Inc.; 🇺🇸 Plantation, Florida, United States

Cancer Specialists of North Florida; 🇺🇸 Saint Augustine, Florida, United States

GenHarp Clinical Solutions; 🇺🇸 Evergreen Park, Illinois, United States

Hematology Oncology Clinic; 🇺🇸 Baton Rouge, Louisiana, United States

New England Cancer Specialists; 🇺🇸 Scarborough, Maine, United States

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

Maryland Oncology Hematology, P.A.; 🇺🇸 Columbia, Maryland, United States

Minnesota Oncology Hematology, P.A.; 🇺🇸 Minneapolis, Minnesota, United States

Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States

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