Colorectal Cancer, CRC, Pancreatic Ductal Adenocarcinoma, PDAC, Gastrointestinal Cancer, Metastatic Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
CRC, PDAC, RAS Mutation, KRAS G12X, Colorectal Cancer, Pancreatic Cancer, Pancreatic Ductal Carcinoma, KRAS Q61 Mutation, KRAS G12 Mutation, RAS Wild-type, RAS G12D Mutation
Brief summary
The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with novel agents. The current subprotocols include the following: Subprotocol A: RMC-6236 + 5-fluorouracil-based regimens Subprotocol B: RMC-6236 + cetuximab with or without mFOLFOX6 Subprotocol C: RMC-6236 + gemcitabine + nab-paclitaxel Subprotocol D: RMC-9805 with or without RMC-6236 + 5-fluorouracil-based regimens Subprotocol E: RMC-9805 with or without RMC-6236 + cetuximab with or without mFOLFOX6 Subprotocol F: RMC-9805 with or without RMC-6236 + gemcitabine + nab-paclitaxel
Detailed description
The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents to be evaluated in patients with RAS-mutated solid tumors with a focus on GI cancers. This is an open-label platform study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC) or with novel agents, and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with RAS mutations will be specified in each subprotocol. Subprotocol A is an open-label, multicenter study of RMC-6236 in combination with 5-fluorouracil-based regimens in patients with treatment-naïve unresectable or metastatic colorectal cancer or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol B is an open-label, multicenter study of RMC-6236 in combination with cetuximab with or without mFOLFOX6 in patients with unresectable or metastatic colorectal cancer or patients with previously treated or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol C is an open-label, multicenter study of RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol D is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with 5-fluorouracil-based regimens in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol E is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with cetuximab-based therapies with or without mFOLFOX6 in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol F is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with RAS G12D-mutant metastatic pancreatic ductal adenocarcinoma. Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.
Interventions
DRUGRMC-6236
Oral tablet
DRUGmFOLFOX6 regimen
IV infusion
DRUGbevacizumab
IV infusion
DRUGmFOLFIRINOX regimen
IV infusion
DRUGcetuximab
IV infusion
DRUGgemcitabine
IV infusion
DRUGnab-paclitaxel
IV infusion
DRUGRMC-9805
Oral Tablet
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
All Patients (unless otherwise noted): * ≥ 18 years of age * ECOG PS is 0 to 1 * Adequate organ function as outlined by the study * Pathologically or cytologically documented pancreatic carcinoma or poorly differentiated pancreatic carcinoma with metastatic disease or RAS-mutated, histologically or cytologically confirmed colorectal adenocarcinoma with documented unresectable or metastatic disease (Subprotocol A, B, and C) * Presence of RAS G12D mutation (Subprotocol D, E, F)
Exclusion criteria
All Patients: * Primary central nervous system (CNS) tumors * Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs * Major surgery within 28 days of first dose Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Up to 3 years | Evaluate the safety and tolerability in the study population characterized by incidence, abnormal laboratory assessments, severity, and seriousness of adverse events in relation to the study treatment. |
| Dose limiting toxicities | 28 days | Number of participants with dose limiting toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of RMC-6236 and RMC-9805 | 21 weeks | Blood concentration of RMC-6236 and RMC-9805 over time |
| ORR | Up to 3 years | Overall Response Rate per RECIST v1.1 |
| DOR | Up to 3 years | Duration of Response per RECIST v1.1 |
| DCR | Up to 3 years | Incidence of Response per RECIST v1.1 |
| TTR | Up to 3 years | Time to Response per RECIST v1.1 |
| PFS | Up to 3 years | Progression Free Survival per RECIST v1.1 |
| OS | Up to 3 years | Overall Survival |
Countries
United States
Contacts
CONTACTRevolution Medicines
STUDY_DIRECTORStudy Director
Revolution Medicines
Outcome results
None listed