Clinical trial NCT05379985: Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS
Official title: A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS
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
Non-small Cell Lung Cancer
Lung Cancer
Colorectal Cancer
Colon Cancer
Metastatic Cancer
Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma
NSCLC
CRC
PDAC
Pancreatic Neoplasms
Carcinoma, Pancreatic Ductal
Colorectal Neoplasms
Colonic Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplastic Processes
Thoracic Neoplasms
Antineoplastic Agents
Melanoma
Gynecological Cancers
RAS
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-18
Enrollment: 614
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.

Detailed description: This is a Phase 1/1b, multicenter open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of escalating doses of RMC-6236 in adult patients with advanced solid tumors harboring specific RAS mutations, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose \[RP2D\] within investigated patient population groups. RMC-6236 is a potent, orally bioavailable RAS-MULTI(ON) inhibitor, selective for the active RAS(ON) form of both wild type and mutant variants of the canonical RAS isoforms (HRAS, NRAS, and KRAS).

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed advanced solid tumor with specific KRAS G12 mutations (dose escalation) or RAS mutations (dose optimization/expansion) identified through deoxyribonucleic acid (DNA) sequencing. PDAC with wild-type RAS (expansion).
* Received prior standard therapy appropriate for tumor type and stage
* Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ function

Exclusion Criteria:

* Primary central nervous system (CNS) tumors
* Active, untreated brain metastases
* Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
* History of any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy

Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs
timeFrame: up to 2.5 years
measure: Number of Participants with Dose-Limiting Toxicity (DLT)
timeFrame: 21 days
Secondary outcomes:
measure: Maximum Observed Blood Concentration (Cmax) of RMC-6236
timeFrame: up to 15 weeks
measure: Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236
timeFrame: up to 15 weeks
measure: Area Under Blood Concentration Time Curve (AUC) of RMC-6236
timeFrame: up to 15 weeks
measure: Elimination Half-Life of RMC-6236 (t1/2)
timeFrame: up to 15 weeks
measure: Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing
timeFrame: up to 15 weeks
measure: Overall Response Rate (ORR)
timeFrame: up to 2.5 years
measure: Duration of Response (DOR)
timeFrame: up to 2.5 years
measure: Disease Control Rate (DCR)
timeFrame: up to 2.5 years
measure: Time to Response (TTR)
timeFrame: up to 2.5 years
measure: Progression-Free Survival (PFS)
timeFrame: up to 2.5 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine/Chao Family Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Perlmutter Cancer Center at NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Cincinnati
country: United States
facility: Christ Hospital Cancer Center
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: University of Texas at Austin
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
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: