Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors
- Conditions
- Advanced Solid TumorNon-Small Cell Lung Cancer (NSCLC)Colorectal Cancer (CRC)Pancreatic Ductal Adenocarcinoma
- Interventions
- Drug: RMC-6291
- Registration Number
- NCT05462717
- Lead Sponsor
- Revolution Medicines, Inc.
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 222
- 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
- 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
Other inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description RMC-6291 RMC-6291 Dose Escalation and Dose Expansion
- Primary Outcome Measures
Name Time Method Adverse events up to 3 years Number of participants with adverse events
Dose Limiting Toxicities The first 21 days (i.e. Cycle 1) Number of participants with dose limiting toxicities
- Secondary Outcome Measures
Name Time Method Maximum Observed Blood Concentration of RMC-6291 7 Cycles Cmax
Time to Reach Maximum Blood Concentration of RMC-6291 7 Cycles Tmax
Area Under Blood Concentration Time Curve of RMC-6291 7 Cycles AUC
Elimination Half-Life of RMC-6291 7 Cycles t1/2
Overall Response Rate (ORR) 3 years Overall response rate per RECIST v1.1
Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing 7 Cycles accumulation ratio
Time to Response (TTR) 3 years Time to response per RECIST v1.1
Progression-Free Survival (PFS) 3 years Progression-free survival per RECIST v1.1
Duration of Response (DOR) 3 years Duration of response per RECIST v1.1
Disease Control Rate (DCR) 3 years Disease control rate per RECIST v1.1
Trial Locations
- Locations (64)
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
University of Miami School of Medicine Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Next Oncology Virginia
🇺🇸Fairfax, Virginia, United States
Southside Cancer Care Centre
🇦🇺Sydney, New South Wales, Australia
MSK Cancer Center
🇺🇸New York, New York, United States
Istituto Europeo Oncologico
🇮🇹Milano, Italy
Peninsula & South Eastern Haematology and Oncology Group
🇦🇺Frankston, Victoria, Australia
Onkologicka klinika, Fakultni Nemocnice Olomouc
🇨🇿Olomouc, Czechia
S.C. Oncologia Falck, Dipartimento Ematologia ed Oncologia Niguarda Cancer Center
🇮🇹Milan, Italy
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Sarawak General Hospital
🇲🇾Kuching, Malaysia
Instytut MSF Sp zoo
🇵🇱Łódź, Poland
E-DA hospital
🇨🇳Kaohsiung, Yanchao District, Taiwan
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
🇮🇹Orbassano, Italy
Centro Ricerche Cliniche di Verona s.r.l.
🇮🇹Verona, Italy
ICO Hospitalet
🇪🇸Barcelona, Spain
Narodowy Instytut Onkologii
🇵🇱Warsaw, Poland
Institute for pulmonary diseases Sremska Kamenica
🇷🇸Sremska Kamenica, Serbia
Ajou University Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
MD Anderson Cancer Center
🇪🇸Madrid, Spain
NH Hospital a.s.
🇨🇿Hořovice, Czechia
Med - Polonia Sp. z o. o.
🇵🇱Poznań, Poland
MSB General Hospital
🇷🇸Belgrade, Serbia
National Cancer centre Singapore
🇸🇬Singapore, Singapore
South West Health Care
🇦🇺Warrnambool, Victoria, Australia
NEXT Oncology IOB Hospital Quirónsalud
🇪🇸Barcelona, Spain
ICANS
🇫🇷Strasbourg, France
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Korea University Hospital
🇰🇷Seoul, Korea, Republic of
Clínica Universidad de Navarra
🇪🇸Madrid, Spain
Hospital Universitario Quirónsalud
🇪🇸Pozuelo De Alarcón, Spain
Clinical hospital center Bezanijska Kosa
🇷🇸Belgrade, Serbia
Taipei Tzu Chi Hospital
🇨🇳New Taipei City, Taiwan
Siriraj Hospital
🇹🇭Bangkok Noi, Thailand
Chiang Mai University
🇹🇭Chiang Mai, Thailand
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Centre Léon Bérard
🇫🇷Lyon, France
ICO
🇫🇷Angers, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
UCSF
🇺🇸San Francisco, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
American Oncology Partners of Maryland
🇺🇸Bethesda, Maryland, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Next Oncology
🇺🇸San Antonio, Texas, United States
CHU Nantes
🇫🇷Nantes, France
UC Davis Cancer Center
🇺🇸Sacramento, California, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
UC Irvine Cancer Center
🇺🇸Orange, California, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
START
🇺🇸San Antonio, Texas, United States
Austin Health, Olivia Newton-John Cancer Research & Wellness Centre
🇦🇺Heidelberg, Victoria, Australia
Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove
🇨🇿Hradec Králové, Czechia
CHU Bordeaux Hospital Saint-Andre
🇫🇷Bordeaux, France
Centre Oscar Lambret
🇫🇷Lille, France
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Khon Kaen University
🇹🇭Khon Kaen, Thailand