Clinical trial NCT06445062: Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
Official title: A Platform Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
CRC
Pancreatic Ductal Adenocarcinoma
PDAC
Gastrointestinal Cancer
Metastatic Pancreatic Ductal Adenocarcinoma
Keywords: CRC
PDAC
RAS Mutation
KRAS G12X
Colorectal Cancer
Pancreatic Cancer
Pancreatic Ductal Carcinoma
KRAS Q61 Mutation
KRAS G12 Mutation
RAS Wild-type
RAS G12D Mutation
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2024-06-06
Enrollment: 1130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with novel agents.

The current subprotocols include the following:

Subprotocol A: RMC-6236 + 5-fluorouracil-based regimens

Subprotocol B: RMC-6236 + cetuximab with or without mFOLFOX6

Subprotocol C: RMC-6236 + gemcitabine + nab-paclitaxel

Subprotocol D: RMC-9805 with or without RMC-6236 + 5-fluorouracil-based regimens

Subprotocol E: RMC-9805 with or without RMC-6236 + cetuximab with or without mFOLFOX6

Subprotocol F: RMC-9805 with or without RMC-6236 + gemcitabine + nab-paclitaxel

Detailed description: The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents to be evaluated in patients with RAS-mutated solid tumors with a focus on GI cancers.

This is an open-label platform study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC) or with novel agents, and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with RAS mutations will be specified in each subprotocol.

Subprotocol A is an open-label, multicenter study of RMC-6236 in combination with 5-fluorouracil-based regimens in patients with treatment-naïve unresectable or metastatic colorectal cancer or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol B is an open-label, multicenter study of RMC-6236 in combination with cetuximab with or without mFOLFOX6 in patients with unresectable or metastatic colorectal cancer or patients with previously treated or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol C is an open-label, multicenter study of RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol D is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with 5-fluorouracil-based regimens in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol E is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with cetuximab-based therapies with or without mFOLFOX6 in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol F is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with RAS G12D-mutant metastatic pancreatic ductal adenocarcinoma.

Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Eligibility criteria: Inclusion Criteria:

All Patients (unless otherwise noted):

* ≥ 18 years of age
* ECOG PS is 0 to 1
* Adequate organ function as outlined by the study
* Pathologically or cytologically documented pancreatic carcinoma or poorly differentiated pancreatic carcinoma with metastatic disease or RAS-mutated, histologically or cytologically confirmed colorectal adenocarcinoma with documented unresectable or metastatic disease (Subprotocol A, B, and C)
* Presence of RAS G12D mutation (Subprotocol D, E, F)

Exclusion Criteria:

All Patients:

* Primary central nervous system (CNS) tumors
* Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
* Major surgery within 28 days of first dose

Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Adverse events
timeFrame: Up to 3 years
measure: Dose limiting toxicities
timeFrame: 28 days
Secondary outcomes:
measure: Pharmacokinetics of RMC-6236 and RMC-9805
timeFrame: 21 weeks
measure: ORR
timeFrame: Up to 3 years
measure: DOR
timeFrame: Up to 3 years
measure: DCR
timeFrame: Up to 3 years
measure: TTR
timeFrame: Up to 3 years
measure: PFS
timeFrame: Up to 3 years
measure: OS
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology- Santa Monica
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital-Anschutz Cancer Pavilion
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Main Campus
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: NEXT Oncology Dallas
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Revolution Medicines
name: Study Director
role: STUDY_DIRECTOR
References: