Clinical trial NCT06128551: Study of RMC-6291 in Combination with RMC-6236 in Participants with Advanced KRAS G12C Mutant Solid Tumors
Official title: Phase 1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 in Combination with RMC-6236 in Participants with Advanced KRAS G12C Mutant Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Colorectal Cancer
Pancreatic Ductal Adenocarcinoma
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
RMC-6236
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2023-11-13
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 125
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the safety, tolerability, and PK profiles of RMC-6291 and RMC-6236 in adults with KRAS G12C-mutated solid tumors.

Detailed description: This is an open-label, multicenter, Phase 1b study of RMC-6291 in combination with RMC-6236 in participants with advanced KRAS G12C-mutated solid tumors, to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose and schedule (RP2DS) and provide a preliminary assessment of the antitumor activity of RMC-6291 in participants with KRASG12C tumors.

The study consists of two parts: Part 1 - Dose-Escalation and Part 2 Dose-Expansion.

Eligibility criteria: Inclusion Criteria:

* 18 years of age
* Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy

  1. Part 1. Dose Escalation: solid tumors, previously treated
  2. Part 2. Dose Expansion:

  i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors, ii. NSCLC, previously treated with immunotherapy and chemotherapy, naïve to KRAS G12C (OFF) inhibitors, iii. NSCLC, previously treated with immunotherapy, chemotherapy, with untreated, asymptomatic central nervous system (CNS) metastases \<2 cm in size iv. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.
* ECOG performance status 0 or 1
* 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

Primary outcomes:
measure: Adverse events
timeFrame: up to 3 years
measure: Dose Limiting Toxicities
timeFrame: 21 days
Secondary outcomes:
measure: Maximum Observed Blood Concentration of RMC-6291 and RMC-6236
timeFrame: up to 21 weeks
measure: Time to Reach Maximum Blood Concentration of RMC-6291 and RMC-6236
timeFrame: up to 21 weeks
measure: Area Under Blood Concentration Time Curve of RMC-6291 and RMC-6236
timeFrame: up to 21 weeks
measure: Elimination Half-Life of RMC-6291 and RMC-6236
timeFrame: up to 21 weeks
measure: Ratio of accumulation of RMC-6291 and RMC-6236 from a single dose to steady state with repeated dosing
timeFrame: up to 21 weeks
measure: Overall Response Rate (ORR)
timeFrame: up to 3 years
measure: Duration of Response (DOR)
timeFrame: up to 3 years
measure: Disease Control Rate
timeFrame: up to 3 years
measure: Time to Response (TTR)
timeFrame: up to 3 years
measure: Progression-Free Survival (PFS)
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Orange
country: United States
facility: UC IRVINE Health
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center and Research Institute
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Cancer
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institue
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Irving
country: United States
facility: NEXT Dallas
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology San Antonio
state: Texas
city: San Antonio
country: United States
facility: START Texas
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Angers
country: France
facility: West Cancer Institute
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bron
country: France
facility: Hospital Louise Pradel
city: Lille
country: France
facility: Oscar Lambret Center of Lillle
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Cancer Institute of Montpellier
city: Nantes
country: France
facility: CHU Nantes
city: Strasbourg
country: France
facility: Institute of Cancer of Strasbourg
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH
city: Köln
country: Germany
facility: Universitäts Klinikum Köln
city: Moers
country: Germany
facility: Krankenhaus Bethanien Moers
city: Nurnberg
country: Germany
facility: Klinkum Nurnberg Paracelsus Medical Unviersity
city: Ancona
country: Italy
facility: Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
city: Meldola
country: Italy
facility: Institute Romagnolo per lo Studio Tumori
city: Milano
country: Italy
facility: Niguarda Cancer Center
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"
city: Orbassano
country: Italy
facility: San Luigi Hospital
city: Ravenna
country: Italy
facility: AUSL Romagna - S.M. delle Croci Hospital
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute Antoni van Leeuwenhoek
city: San Juan
country: Puerto Rico
facility: Pan American Center for Oncology Trials
city: Barcelona
country: Spain
facility: START Barcelona - Hospital HM Nou Delfos
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia Hospital
city: Madrid
country: Spain
facility: University Clinic of Navarra
city: Madrid
country: Spain
facility: Fundacion MD Anderson Cancer Center
city: Madrid
country: Spain
facility: START Madrid
city: Madrid
country: Spain
facility: Hosptial Universitario 12 de Octubre
city: Madrid
country: Spain
facility: NEXT Oncology - Quirónsalud Madrid University Hospital
city: Pamplona
country: Spain
facility: University Clinic of Navarra
city: Sevilla
country: Spain
facility: Hosptial Universitario Virgen Macarena
city: Valencia
country: Spain
facility: La Fe University and Polytechnic Hospital
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
Study officials:
affiliation: Revolution Medicines, Inc.
name: Revolution Medicines, Inc.
role: STUDY_DIRECTOR
References: