The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant solid tumors.
This is an open-label, multicenter, Phase 1/1b study of RMC-5127 in adults with advanced KRAS G12V-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: RMC-5127 monotherapy arm, RMC-5127 plus daraxonrasib combination arm, and RMC-5127 plus cetuximab combination arm. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Both parts of the monotherapy arm may include Food Effect Cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
574
Yale Cancer Center
New Haven, Connecticut, United States
RECRUITINGJohns Hopkins
Baltimore, Maryland, United States
RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGSTART Midwest
Grand Rapids, Michigan, United States
RECRUITINGLaura and Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, United States
RECRUITINGNEXT - Dallas
Dallas, Texas, United States
RECRUITINGNEXT
San Antonio, Texas, United States
RECRUITINGSTART - San Antonio
San Antonio, Texas, United States
RECRUITINGNEXT - Virginia
Fairfax, Virginia, United States
RECRUITINGNumber of patients with adverse events (AEs)
Number of patients with AEs as assessed by Common Terminology Criteria for Adverse Events CTCAE v5
Time frame: Up to approximately 3 years
Changes in vital signs
Number of patients with changes from baseline in vital signs
Time frame: Up to approximately 3 years
Changes in electrocardiogram (ECG) test values
Number of patients with changes from baseline in ECG test values
Time frame: Up to approximately 3 years
Changes in clinical laboratory test values
Number of patients with changes from baseline in clinical laboratory test values
Time frame: Up to approximately 3 years
Dose Limiting Toxicities
Number of patients with dose limiting toxicities
Time frame: Up to 28 days
Cmax concentrations of RMC-5127 and daraxonrasib
Maximum blood concentration (Cmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Cmax of daraxonrasib in combination with RMC-5127 over time as applicable
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Tmax concentration of RMC-5127 and daraxonrasib
Time to reach maximum blood concentration (Tmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Tmax of daraxonrasib in combination with RMC-5127 over time as applicable
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
AUC concentrations of RMC-5127 and daraxonrasib
Area under the blood concentration time curve (AUC) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and AUC of daraxonrasib in combination with RMC-5127 over time as applicable
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Ratio of accumulation of RMC-5127
Ratio of accumulation of RMC-5127 from a single dose to steady state with repeated dosing as monotherapy and in combination with darabxrasib or cetuximab over time as applicable
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Half-Life of RMC-5127 and daraxonrasib
Elimination Half-Life (t1/2) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and t1/2 of daraxonrasib in combination with RMC-5127 over time as applicable
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Objective Response Rate (ORR)
ORR per response evaluation criteria in solid tumors (RECIST) v1.1
Time frame: Up to approximately 3 years
Duration of Response (DOR)
DOR per RECIST v1.1
Time frame: Up to approximately 3 years
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