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

NCT ID: NCT05462717

Last Updated: 2024-11-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

222 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-19

Study Completion Date

2025-12-31

Brief Summary

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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

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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.

Conditions

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Non-Small Cell Lung Cancer (NSCLC) Colorectal Cancer (CRC) Pancreatic Ductal Adenocarcinoma Advanced Solid Tumor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RMC-6291

Dose Escalation and Dose Expansion

Group Type EXPERIMENTAL

RMC-6291

Intervention Type DRUG

Oral tablet once or twice a day

Interventions

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RMC-6291

Oral tablet once or twice a day

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Revolution Medicines, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Revolution Medicines, Inc.

Role: STUDY_DIRECTOR

Revolution Medicines, Inc.

Locations

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Highlands Oncology Group

Springdale, Arkansas, United States

Site Status

UC Irvine Cancer Center

Orange, California, United States

Site Status

UC Davis Cancer Center

Sacramento, California, United States

Site Status

UCSF

San Francisco, California, United States

Site Status

University of Miami School of Medicine Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

American Oncology Partners of Maryland

Bethesda, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

MSK Cancer Center

New York, New York, United States

Site Status

Columbia University Irving Medical Center

New York, New York, United States

Site Status

Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Next Oncology

San Antonio, Texas, United States

Site Status

START

San Antonio, Texas, United States

Site Status

Next Oncology Virginia

Fairfax, Virginia, United States

Site Status

Southside Cancer Care Centre

Sydney, New South Wales, Australia

Site Status

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Site Status

Austin Health, Olivia Newton-John Cancer Research & Wellness Centre

Heidelberg, Victoria, Australia

Site Status

South West Health Care

Warrnambool, Victoria, Australia

Site Status

NH Hospital a.s.

Hořovice, , Czechia

Site Status

Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove

Hradec Králové, , Czechia

Site Status

Onkologicka klinika, Fakultni Nemocnice Olomouc

Olomouc, , Czechia

Site Status

ICO

Angers, , France

Site Status

CHU Bordeaux Hospital Saint-Andre

Bordeaux, , France

Site Status

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

CHU Nantes

Nantes, , France

Site Status

ICANS

Strasbourg, , France

Site Status

S.C. Oncologia Falck, Dipartimento Ematologia ed Oncologia Niguarda Cancer Center

Milan, , Italy

Site Status

Istituto Europeo Oncologico

Milan, , Italy

Site Status

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, , Italy

Site Status

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, , Italy

Site Status

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status

Centro Ricerche Cliniche di Verona s.r.l.

Verona, , Italy

Site Status

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status

Sarawak General Hospital

Kuching, , Malaysia

Site Status

Instytut MSF Sp zoo

Lodz, , Poland

Site Status

Med - Polonia Sp. z o. o.

Poznan, , Poland

Site Status

Narodowy Instytut Onkologii

Warsaw, , Poland

Site Status

MSB General Hospital

Belgrade, , Serbia

Site Status

Clinical hospital center Bezanijska Kosa

Belgrade, , Serbia

Site Status

Institute for pulmonary diseases Sremska Kamenica

Kamenitz, , Serbia

Site Status

National Cancer centre Singapore

Singapore, , Singapore

Site Status

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea

Site Status

Korea University Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital

Seoul, , South Korea

Site Status

NEXT Oncology IOB Hospital Quirónsalud

Barcelona, , Spain

Site Status

ICO Hospitalet

Barcelona, , Spain

Site Status

Clínica Universidad de Navarra

Madrid, , Spain

Site Status

MD Anderson Cancer Center

Madrid, , Spain

Site Status

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status

Hospital Universitario Quirónsalud

Pozuelo de Alarcón, , Spain

Site Status

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

E-DA hospital

Kaohsiung City, Yanchao District, Taiwan

Site Status

Taipei Tzu Chi Hospital

New Taipei City, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Siriraj Hospital

Bangkok Noi, , Thailand

Site Status

Chiang Mai University

Chiang Mai, , Thailand

Site Status

Khon Kaen University

Khon Kaen, , Thailand

Site Status

Countries

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United States Australia Czechia France Italy Malaysia Poland Serbia Singapore South Korea Spain Taiwan Thailand

References

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Schulze CJ, Seamon KJ, Zhao Y, Yang YC, Cregg J, Kim D, Tomlinson A, Choy TJ, Wang Z, Sang B, Pourfarjam Y, Lucas J, Cuevas-Navarro A, Ayala-Santos C, Vides A, Li C, Marquez A, Zhong M, Vemulapalli V, Weller C, Gould A, Whalen DM, Salvador A, Milin A, Saldajeno-Concar M, Dinglasan N, Chen A, Evans J, Knox JE, Koltun ES, Singh M, Nichols R, Wildes D, Gill AL, Smith JAM, Lito P. Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS. Science. 2023 Aug 18;381(6659):794-799. doi: 10.1126/science.adg9652. Epub 2023 Aug 17.

Reference Type DERIVED
PMID: 37590355 (View on PubMed)

Other Identifiers

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RMC-6291-001

Identifier Type: -

Identifier Source: org_study_id

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