Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Adenocarcinoma, Pancreatic Ductal Adenocarcinoma (PDAC), PDAC, CRC, NSCLC, Pancreatic Cancer, Lung Cancer (NSCLC), Advanced Solid Tumors
Conditions
Keywords
Advanced Solid Tumors, Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, PDAC, Colorectal Cancer, CRC, Lung Cancer, Non-small Cell Lung Cancer, NSCLC, RAS, KRAS, RAS Mutation
Brief summary
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.
Detailed description
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.
Interventions
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old and has provided informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Pathologically documented, locally advanced or metastatic KRAS G12V-mutated solid tumor malignancy. * Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage. * Measurable per RECIST v1.1 * Adequate organ function (bone marrow, liver, kidney, coagulation). * Able to take oral medications.
Exclusion criteria
* Primary central nervous system (CNS) tumors * Prior therapy with KRAS G12V inhibitor or direct RAS-targeted therapy (eg. degraders and/or inhibitors). * Any conditions that may affect the ability to take or absorb study drug. * Major surgery within 28 days prior to receiving study drug(s). * Patient is unable or unwilling to comply with protocol-required study visits or procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities | Up to 28 days | Number of patients with dose limiting toxicities |
| Number of patients with adverse events (AEs) | Up to approximately 3 years | Number of patients with AEs as assessed by Common Terminology Criteria for Adverse Events CTCAE v5 |
| Changes in vital signs | Up to approximately 3 years | Number of patients with changes from baseline in vital signs |
| Changes in electrocardiogram (ECG) test values | Up to approximately 3 years | Number of patients with changes from baseline in ECG test values |
| Changes in clinical laboratory test values | Up to approximately 3 years | Number of patients with changes from baseline in clinical laboratory test values |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax concentrations of RMC-5127 and daraxonrasib | Up to Cycle 5 Day 1 (each cycle is up to 28 days) | 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 |
| Tmax concentration of RMC-5127 and daraxonrasib | Up to Cycle 5 Day 1 (each cycle is up to 28 days) | 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 |
| AUC concentrations of RMC-5127 and daraxonrasib | Up to Cycle 5 Day 1 (each cycle is up to 28 days) | 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 |
| Ratio of accumulation of RMC-5127 | Up to Cycle 5 Day 1 (each cycle is up to 28 days) | 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 |
| Half-Life of RMC-5127 and daraxonrasib | Up to Cycle 5 Day 1 (each cycle is up to 28 days) | 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 |
| Objective Response Rate (ORR) | Up to approximately 3 years | ORR per response evaluation criteria in solid tumors (RECIST) v1.1 |
| Duration of Response (DOR) | Up to approximately 3 years | DOR per RECIST v1.1 |
Countries
United States
Contacts
CONTACTRevolution Medicines Study Director
Outcome results
None listed