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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
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.

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
GroupInterventionDescription
RMC-4630 and sotorasib, Safety Run-inRMC-4630Safety Run-In: RMC-4630 and sotorasib
RMC-4630 and sotorasib, Safety Run-inSotorasibSafety Run-In: RMC-4630 and sotorasib
RMC-4630 and sotorasib, ExpansionRMC-4630Dose Expansion: RMC-4630 and sotorasib
RMC-4630 and sotorasib, ExpansionSotorasibDose Expansion: RMC-4630 and sotorasib
Primary Outcome Measures
NameTimeMethod
Objective response rate (ORR)approximately 12 months

ORR as assessed per RECIST v1.1

Secondary Outcome Measures
NameTimeMethod
Concentration of sotorasibapproximately 12 months

Trough Concentration of sotorasib

Vital signsapproximately 12 months

Number of subjects with clinically significant changes in vital signs

ECGs Measurementsapproximately 12 months

Number of subjects with clinically significant changes in ECGs Measurements

Serious Adverse Eventsapproximately 12 months

Number of Participants with Serious Adverse Events

Overall survival (OS)approximately 12 months

Overall survival (OS)

Clinical laboratory test valuesapproximately 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 Eventsapproximately 12 months

Number of Participants with Adverse Events

Concentration of RMC-4630approximately 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

Trial Locations

Locations (59)

Florida Cancer Specialists

🇺🇸

Fort Myers, Florida, United States

BRCR Medical Center Inc.

🇺🇸

Plantation, Florida, United States

Hematology Oncology Clinic

🇺🇸

Baton Rouge, Louisiana, United States

New England Cancer Specialists

🇺🇸

Scarborough, Maine, United States

Cancer Specialists of North Florida

🇺🇸

Saint Augustine, Florida, United States

Maryland Oncology Hematology, P.A.

🇺🇸

Columbia, Maryland, United States

New Jersey Center for Cancer Research

🇺🇸

Brick, New Jersey, United States

Charleston Oncology

🇺🇸

Charleston, South Carolina, United States

Tennessee Oncology

🇺🇸

Chattanooga, Tennessee, United States

South West Oncology

🇦🇺

Warrnambool, Victoria, Australia

William Osler Health System

🇨🇦

Mississauga, Ontario, Canada

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

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

🇫🇷

Marseille, France

Asklepios Fachkliniken Munchen

🇩🇪

Gauting, Bavaria, Germany

Lungenklinik Hemer

🇩🇪

Hemer, North Rhine- Westphalia, Germany

Charite Benjamin Franklin Comprehensive Cancer center

🇩🇪

Berlin, Germany

Evangelische Lung Clinic

🇩🇪

Berlin, Germany

Hamato-Onkologie Hamburg

🇩🇪

Hamburg, Germany

Azienda Ospedaliera dei Colli

🇮🇹

Napoli, Campania, Italy

Istituto Europeo Di Oncologia

🇮🇹

Milano, Italy

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Taichung Veterans General Hospital

🇨🇳

Taichung, Taiwan

The Royal Marsden NHS Foundation Trust

🇬🇧

Sutton, Surrey, United Kingdom

Bethanien Hospital Moers

🇩🇪

Moers, North Rhine-Westphalia, Germany

Lung Cancer Center, University of Saarland

🇩🇪

Homburg, Saarland, Germany

Minnesota Oncology Hematology, P.A.

🇺🇸

Minneapolis, Minnesota, United States

Sarah Cannon Research Institute

🇺🇸

Nashville, Tennessee, United States

Comprehensive Cancer Centers of Nevada

🇺🇸

Las Vegas, Nevada, United States

American Oncology Partners of Maryland, PA

🇺🇸

Bethesda, Maryland, United States

Nebraska Cancer Specialists

🇺🇸

Omaha, Nebraska, United States

GenHarp Clinical Solutions

🇺🇸

Evergreen Park, Illinois, United States

University of New Mexico Comprehensive Cancer Center

🇺🇸

Albuquerque, New Mexico, United States

Clinical Research Alliance, Inc.

🇺🇸

New York, New York, United States

Roswell Park cancer Institute

🇺🇸

Buffalo, New York, United States

Zangmeister Cancer Center

🇺🇸

Columbus, Ohio, United States

Virginia Oncology Associates

🇺🇸

Norfolk, Virginia, United States

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

🇺🇸

Texarkana, Texas, United States

Virginia Cancer Specialists

🇺🇸

Fairfax, Virginia, United States

Blacktown Hospital

🇦🇺

Blacktown, Australia

Goulburn Valley Health

🇦🇺

Shepparton, Australia

Northwest Cancer specialists, P.C.

🇺🇸

Vancouver, Washington, United States

Hospital Larrey Universite Paul Sabatier

🇫🇷

Toulouse, France

Klinikum Esslingen GmbH

🇩🇪

Esslingen, Baden-Wurttemberg, Germany

Comprehensive Cancer Center Mainfranken, University Wuerzburg

🇩🇪

Homburg, Saarland, Germany

POIS Sachsen GmbH

🇩🇪

Leipzig, Sachsen, Germany

Azienda Sanitaria Ospedaliera S Luigi Gonzaga

🇮🇹

Orbassano, Piedmont, Italy

Chungbuk National University Hospital

🇰🇷

Cheongju-si, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Complejo Hospitalario Universitario A Coruña

🇪🇸

A Coruña, Galicia, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Andalucia, Spain

Clinica Universidad de Navarra

🇪🇸

Madrid, Spain

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Catalonia, Spain

Hospital Universitario y Politecnico La Fe

🇪🇸

Valencia, Spain

Kaohsiung Medical University Chung Ho Memorial Hospital

🇨🇳

Kaohsiung, Taiwan

E-DA Hospital

🇨🇳

Kaohsiung, Taiwan

National Cheng Kung University Hospital

🇨🇳

Tainan, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

The Christie NHS Foundation Trust

🇬🇧

Manchester, Greater Manchester, United Kingdom

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