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

NCT05462717 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: RMC-6291-001
• Study Type: interventional
• Target: 222
• Locations: 13 countries
• Sites: 64

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.

Conditions

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

Keywords

RMC-6291; RAS(ON); KRAS; KRASG12C; KRASG12C(ON); Targeted therapy; Metastatic cancer; Lung Cancer; Lung Neoplasms; Thoracic Neoplasms; Non-small Cell Lung Cancer; Carcinoma, Non-Small Cell Lung; NSCLC; Colorectal Cancer; Colonic Neoplasms; CRC; Appendiceal Cancer; KRAS mutation; STK11/LKB1; KEAP1; bronchial neoplasms; respiratory tract neoplasms; neoplasms by site; neoplasms; Colon Cancer; Rectal Cancer; lung disease; respiratory tract diseases; Pancreatic Cancer; Carcinoma, Pancreatic Ductal; PDAC; Gastrointestinal Neoplasms; Intestinal Neoplasms; Esophageal cancer; Ampullary cancer; Gastric Cancer; Gynecological Cancer; Ovarian Cancer; Endometrial Cancer

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Number of participants with adverse events

  up to 3 years

• Dose Limiting Toxicities

  Number of participants with dose limiting toxicities

  The first 21 days (i.e. Cycle 1)

Secondary Outcomes (10)

• Maximum Observed Blood Concentration of RMC-6291

  7 Cycles

• Time to Reach Maximum Blood Concentration of RMC-6291

  7 Cycles

• Area Under Blood Concentration Time Curve of RMC-6291

  7 Cycles

• Elimination Half-Life of RMC-6291

  7 Cycles

• Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing

  7 Cycles

Study Arms (1)

RMC-6291

EXPERIMENTAL

Dose Escalation and Dose Expansion

Drug: RMC-6291

Interventions

RMC-6291 DRUG

Oral tablet once or twice a day

RMC-6291

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-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 and for NSCLC in dose expansion
• Adequate organ function

You may not qualify if:

• 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

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead

Study Sites (64)

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

UC Irvine Cancer Center

Orange, California, 92868, United States

Location

UC Davis Cancer Center

Sacramento, California, 95817, United States

Location

UCSF

San Francisco, California, 94158, United States

Location

University of Miami School of Medicine Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

American Oncology Partners of Maryland

Bethesda, Maryland, 20817, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

MSK Cancer Center

New York, New York, 10021, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Next Oncology

San Antonio, Texas, 78229, United States

Location

START

San Antonio, Texas, 78229, United States

Location

Next Oncology Virginia

Fairfax, Virginia, 22031, United States

Location

Southside Cancer Care Centre

Sydney, New South Wales, 2228, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

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

Heidelberg, Victoria, 3084, Australia

Location

South West Health Care

Warrnambool, Victoria, 3280, Australia

Location

NH Hospital a.s.

Hořovice, 268 31, Czechia

Location

Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove

Hradec Králové, 50005, Czechia

Location

Onkologicka klinika, Fakultni Nemocnice Olomouc

Olomouc, 77900, Czechia

Location

ICO

Angers, 49055, France

Location

CHU Bordeaux Hospital Saint-Andre

Bordeaux, 33000, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

CHU Nantes

Nantes, 44093, France

Location

ICANS

Strasbourg, 67200, France

Location

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

Milan, 20162, Italy

Location

Istituto Europeo Oncologico

Milan, 20141, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale

Naples, 80131, Italy

Location

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, 10043, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Centro Ricerche Cliniche di Verona s.r.l.

Verona, 37134, Italy

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Sarawak General Hospital

Kuching, 93586, Malaysia

Location

Instytut MSF Sp zoo

Lodz, 90-302, Poland

Location

Med - Polonia Sp. z o. o.

Poznan, 60-693, Poland

Location

Narodowy Instytut Onkologii

Warsaw, 02-781, Poland

Location

MSB General Hospital

Belgrade, 11000, Serbia

Location

Clinical hospital center Bezanijska Kosa

Belgrade, 11071, Serbia

Location

Institute for pulmonary diseases Sremska Kamenica

Kamenitz, 21204, Serbia

Location

National Cancer centre Singapore

Singapore, 168583, Singapore

Location

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

Location

Korea University Hospital

Seoul, 02708, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Severance Hospital

Seoul, 3722, South Korea

Location

NEXT Oncology IOB Hospital Quirónsalud

Barcelona, 08023, Spain

Location

ICO Hospitalet

Barcelona, 08908, Spain

Location

Clínica Universidad de Navarra

Madrid, 28027, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario Quirónsalud

Pozuelo de Alarcón, 28223, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

E-DA hospital

Kaohsiung City, Yanchao District, 82445, Taiwan

Location

Taipei Tzu Chi Hospital

New Taipei City, 231, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70457, Taiwan

Location

National Taiwan University Hospital

Taipei, 10048, Taiwan

Location

Siriraj Hospital

Bangkok Noi, 10700, Thailand

Location

Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Khon Kaen University

Khon Kaen, 40002, Thailand

Location

Related Publications (1)

• 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.

  PMID: 37590355 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Neoplasm Metastasis; Lung Neoplasms; Thoracic Neoplasms; Colonic Neoplasms; Appendiceal Neoplasms; Bronchial Neoplasms; Respiratory Tract Neoplasms; Neoplasms by Site; Neoplasms; Rectal Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Gastrointestinal Neoplasms; Intestinal Neoplasms; Esophageal Neoplasms; Stomach Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cecal Neoplasms; Cecal Diseases; Bronchial Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary; Head and Neck Neoplasms; Esophageal Diseases; Stomach Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Study Officials

• Revolution Medicines, Inc.

  Revolution Medicines, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 18, 2022
• Study Start: September 19, 2022
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (4); MY (2); IT (6); KR (4); US (15); CZ (3); AU (4); ES (9); TH (3); FR (7); SG (1); SE (3); PL (3)