Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: RMC-6236, mFOLFOX6 regimen, bevacizumab, mFOLFIRINOX regimen.
- Who it may be relevant to
- Registry conditions: Colorectal Cancer, CRC, Pancreatic Ductal Adenocarcinoma, PDAC. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Platform Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors
Overview
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
- Drug RMC-6236
Oral tablet - Drug mFOLFOX6 regimen
IV infusion - Drug bevacizumab
IV infusion - Drug mFOLFIRINOX regimen
IV infusion - Drug cetuximab
IV infusion - Drug gemcitabine
IV infusion - Drug nab-paclitaxel
IV infusion - Drug RMC-9805
Oral Tablet
Primary outcome measures
- Adverse events [Time frame: Up to 3 years]
- Dose limiting toxicities [Time frame: 28 days]
Secondary outcome measures (7)
- Pharmacokinetics of RMC-6236 and RMC-9805 [Time frame: 21 weeks]
- ORR [Time frame: Up to 3 years]
- DOR [Time frame: Up to 3 years]
- DCR [Time frame: Up to 3 years]
- TTR [Time frame: Up to 3 years]
- PFS [Time frame: Up to 3 years]
- OS [Time frame: Up to 3 years]
Eligibility criteria
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/exclusion criteria may apply.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 32 centers
- Ironwood Cancer and Research Centers — Chandler
- Mayo Clinic Hospital — Phoenix
- HonorHealth Research Institute — Scottsdale
- UC San Diego Moores Cancer Center — La Jolla
- Cedars-Sinai Cancer at Cedars-Sinai Medical Center — Los Angeles
- UCLA Hematology/Oncology- Santa Monica — Los Angeles
- University of Colorado Hospital-Anschutz Cancer Pavilion — Aurora
- Yale-New Haven Hospital-Yale Cancer Center — New Haven
- … and 24 more centers
Publications
- Cregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J PMID 40056080
Identifiers
NCT: NCT06445062 · RMC-GI-102