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
START Midwest
Grand Rapids, Michigan, 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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