Clinical trial NCT06040541: Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors
Official title: Phase 1/1b, Multicenter, Open-Label, Study of RMC 9805 in Participants With Advanced KRASG 12D-Mutant Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer (NSCLC)
Colorectal Cancer (CRC)
Pancreatic Ductal Adenocarcinoma (PDAC)
Advanced Solid Tumors
Keywords: KRAS G12D (ON)
NSCLC
CRC
PDAC
Non-small Cell Lung Cancer
Lung Cancer
Colorectal Cancer
Colon Cancer
Pancreatic Cancer
Metastatic Cancer
Pancreatic Ductal Adenocarcinoma
Pancreatic Neoplasms
Colorectal Neoplasms
Gastrointestinal Neoplasms
KRAS
Colonic Neoplasms
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2023-09-15
Enrollment: 444
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The monotherapy arm of RMC-9805; the combination arm of RMC-9805 plus RMC-6236
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.

Detailed description: This is an open-label, multicenter, Phase 1/1b study of RMC-9805, a selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two arms: RMC-9805 monotherapy arm and RMC-9805 plus RMC-6236 combination arm. Both arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion.

Eligibility criteria: Inclusion Criteria:

* Pathologically documented, locally advanced or metastatic solid tumor with a KRAS G12D-mutation
* Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage
* ECOG performance status 0 or 1
* Adequate organ function

Exclusion Criteria:

* Primary central nervous system (CNS) tumors
* Known or suspected leptomeningeal or active brain metastases or spinal cord compression
* Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
* Participant was previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors)

Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Adverse events
timeFrame: Up to 3 years
measure: Dose Limiting Toxicities
timeFrame: 21 days
Secondary outcomes:
measure: Maximum Observed Blood Concentration (Cmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Cmax of RMC-6236 in combination with RMC-9805
timeFrame: up to 21 weeks
measure: Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Tmax of RMC-6236 in combination with RMC-9805
timeFrame: up to 21 weeks
measure: Area Under Blood Concentration Time Curve (AUC) of RMC-9805 as monotherapy and in combination with RMC-6236, and AUC of RMC-6236 in combination with RMC-9805
timeFrame: up to 21 weeks
measure: Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing as monotherapy and in combination with RMC-6236, and ratio of accumulation of RMC-6236 in combination with RMC-9805
timeFrame: up to 21 weeks
measure: Elimination Half-Life (t1/2) of RMC-9805 as monotherapy and in combination with RMC-6236, and t1/2 of RMC-6236 in combination with RMC-9805
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 (DCR)
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: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital (Yale University)
state: Connecticut
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Lee Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
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: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: START
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
Study officials:
affiliation: Revolution Medicines, Inc.
name: Revolution Medicines, Inc.
role: STUDY_DIRECTOR
References: