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

NCT05054725 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RMC-4630-03
• Study Type: interventional
• Target: 47
• Locations: 10 countries
• Sites: 60

Brief Summary

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

Conditions

Non-Small Cell Lung Cancer

Keywords

SHP2; NSCLC; KRAS G12C; BRAF Class 1/2/unclassified; KRAS amplification; KRAS mutation; STK11/LKB1; KEAP1; PIK3CA; ATRX; BRCA2; carcinoma, non-small lung cancer; bronchial neoplasms; lung neoplasms; respiratory tract neoplasms; neoplasms by site; neoplasms; lung diseases; respiratory tract diseases

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) as Assessed Per RECIST v1.1

  Evaluation of the antitumor effects of RMC-4630 and sotorasib in locally advanced or metastatic NSCLC patients with KRASG12C mutation with and without co-existing genetic aberrations in specific genes such as STK11/LKB1, KEAP1, and PIK3CA after failure of prior standard therapy. Objective Response Rate (%) is defined as the proportion of patients with Best Overall Response of confirmed CR, or PR. Response was confirmed by a repeat assessment no less than 28 days.

  31 months

Secondary Outcomes (10)

• Clinically Significant Changes in Vital Signs

  31 months

• Clinically Significant Changes in Laboratory Tests

  31 months

• Clinically Significant Changes in ECGs

  31 months

• Trough and Approximate Peak Concentrations of RMC-4630

  31 months

• Trough and Approximate Peak Concentrations of Sotorasib

  31 months

Study Arms (2)

RMC-4630 and sotorasib, Safety Run-in

EXPERIMENTAL

Safety Run-In: RMC-4630 and sotorasib

Drug: RMC-4630; Drug: Sotorasib

RMC-4630 and sotorasib, Expansion

EXPERIMENTAL

Dose Expansion: RMC-4630 and sotorasib

Drug: RMC-4630; Drug: Sotorasib

Interventions

RMC-4630 DRUG

RMC-4630 administered orally as a capsule

Also known as: SAR442720

RMC-4630 and sotorasib, Expansion; RMC-4630 and sotorasib, Safety Run-in

Sotorasib DRUG

Sotorasib administered orally as a tablet

Also known as: AMG 510, Lumakras

RMC-4630 and sotorasib, Expansion; RMC-4630 and sotorasib, Safety Run-in

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead
• Sanofi: collaborator
• Amgen: collaborator

Study Sites (60)

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

BRCR Medical Center Inc.

Plantation, Florida, 33322, United States

Location

Cancer Specialists of North Florida

Saint Augustine, Florida, 32086, United States

Location

GenHarp Clinical Solutions

Evergreen Park, Illinois, 60805, United States

Location

Hematology Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817, United States

Location

Maryland Oncology Hematology, P.A.

Columbia, Maryland, 21044, United States

Location

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, 55404, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

New Jersey Center for Cancer Research

Brick, New Jersey, 08724, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Roswell Park cancer Institute

Buffalo, New York, 14263, United States

Location

Clinical Research Alliance, Inc.

New York, New York, 10021, United States

Location

Zangmeister Cancer Center

Columbus, Ohio, 43219, United States

Location

Charleston Oncology

Charleston, South Carolina, 29414, United States

Location

Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

CHRISTUS St. Michael-Colom and Carney Clinic P.A

Texarkana, Texas, 75503, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Northwest Cancer specialists, P.C.

Vancouver, Washington, 98684, United States

Location

South West Oncology

Warrnambool, Victoria, 3280, Australia

Location

Blacktown Hospital

Blacktown, 2148, Australia

Location

Goulburn Valley Health

Shepparton, 3630, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

William Osler Health System

Mississauga, Ontario, L5N 5M8, Canada

Location

APHM Hopital Nord, Service d'Oncologie Multidisciplinaire et innovations therapeutics

Marseille, 13015, France

Location

Hospital Larrey Universite Paul Sabatier

Toulouse, 31059, France

Location

Klinikum Esslingen GmbH

Esslingen am Neckar, Baden-Wurttemberg, 73730, Germany

Location

Asklepios Fachkliniken Munchen

Gauting, Bavaria, 82131, Germany

Location

Lungenklinik Hemer

Hemer, North Rhine-Westphalia, 58675, Germany

Location

Bethanien Hospital Moers

Moers, North Rhine-Westphalia, 47441, Germany

Location

Comprehensive Cancer Center Mainfranken, University Wuerzburg

Homburg, Saarland, 66421, Germany

Location

Lung Cancer Center, University of Saarland

Homburg, Saarland, 66421, Germany

Location

POIS Sachsen GmbH

Leipzig, Saxony, 04347, Germany

Location

Charite Benjamin Franklin Comprehensive Cancer center

Berlin, 12200, Germany

Location

Evangelische Lung Clinic

Berlin, 13125, Germany

Location

Hamato-Onkologie Hamburg

Hamburg, 20251, Germany

Location

Azienda Ospedaliera dei Colli

Naples, Campania, 80131, Italy

Location

Azienda Sanitaria Ospedaliera S Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

Location

Istituto Europeo Di Oncologia

Milan, 20141, Italy

Location

Chungbuk National University Hospital

Cheongju-si, 28644, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario Virgen Macarena

Seville, Andalusia, 41009, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, Galicia, 15006, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Clinica Universidad de Navarra

Madrid, 28027, Spain

Location

Hospital Universitario y Politecnico La Fe

Valencia, 46026, Spain

Location

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

E-DA Hospital

Kaohsiung City, 824, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Hereditary Sensory and Autonomic Neuropathies; Carcinoma; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Interventions

sotorasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Thoracic Neoplasms; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Bronchial Diseases

Results Point of Contact

• Title: Vice-President Clinical Operations
• Organization: Revolution Medicines

RMC-4630-01@revmed.com

650-779-2300

Study Officials

• Revolution Medicines, Inc.

  Revolution Medicines, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: September 23, 2021
• Study Start: December 30, 2021
• Primary Completion: July 3, 2024
• Study Completion: August 29, 2024
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (23); CA (2); TW (5); FR (2); DE (10); ES (6); AU (3); IT (3); KR (4); GB (2)