TrialFetch AI Analysis
Goal: The goal of this study is to determine whether first-line daraxonrasib, either as monotherapy or combined with gemcitabine plus nab-paclitaxel, improves progression-free survival and/or overall survival compared with standard gemcitabine plus nab-paclitaxel alone in patients with metastatic pancreatic adenocarcinoma. The study will also evaluate safety, antitumor activity, pharmacokinetics, and patient-reported quality of life.
Patients: The trial is enrolling adults with histologically or cytologically confirmed metastatic pancreatic adenocarcinoma diagnosed within 6 weeks before informed consent. Patients must have ECOG performance status 0 or 1, measurable disease by RECIST v1.1, documented RAS mutation status, adequate organ function, and the ability to take oral medication. Key exclusions include prior systemic therapy for metastatic disease, any prior RAS-targeted therapy, untreated CNS metastases, major surgery within 28 days, or conditions that could impair oral drug absorption or protocol compliance.
Design: This is a global, multicenter, open-label, randomized, 3-arm Phase 3 treatment study. Patients are randomized to daraxonrasib monotherapy, daraxonrasib plus gemcitabine and nab-paclitaxel, or gemcitabine and nab-paclitaxel alone. The comparator arm reflects a standard first-line chemotherapy option for metastatic pancreatic adenocarcinoma. Follow-up for efficacy, safety, and quality-of-life outcomes is planned for up to approximately 2 years.
Treatments: Arm A receives daraxonrasib monotherapy. Arm B receives daraxonrasib in combination with gemcitabine and nab-paclitaxel. Arm C receives gemcitabine and nab-paclitaxel, a standard cytotoxic chemotherapy regimen used in the first-line treatment of metastatic pancreatic adenocarcinoma.
Daraxonrasib, also known as RMC-6236, is an investigational oral, noncovalent, macrocyclic RAS(ON) inhibitor designed to target active GTP-bound RAS proteins, including mutant and wild-type RAS. It forms a complex with cyclophilin A that binds active RAS and inhibits downstream RAS signaling pathways involved in tumor growth and survival. In earlier-phase studies in previously treated RAS-mutant metastatic pancreatic ductal adenocarcinoma, daraxonrasib showed encouraging activity, with reported median progression-free survival of 7.6 months and median overall survival of 14.5 months at clinically active doses; manageable safety has also been reported, with rash among the common treatment-related adverse events in other RAS-mutant tumor cohorts.
Outcomes: The primary outcomes are progression-free survival by investigator assessment using RECIST v1.1 and overall survival, both assessed over approximately 2 years. Secondary outcomes include objective response rate, duration of response, daraxonrasib blood concentrations in the daraxonrasib-containing arms, adverse events by CTCAE v5, clinically significant changes in vital signs, laboratory abnormalities, and patient-reported outcomes using the EORTC QLQ-PAN26 and EORTC QLQ-C30 instruments.
Burden on patient: The overall patient burden is expected to be moderate. Treatment requires regular oncology visits for chemotherapy infusions in the combination and control arms, while daraxonrasib is an oral agent that adds daily medication adherence requirements and additional monitoring. Patients in the daraxonrasib arms will undergo pharmacokinetic blood sampling through Cycle 5 Day 1, along with routine safety laboratory testing, vital signs, imaging assessments, and quality-of-life questionnaires. The trial does not specify mandatory research biopsies, and the assessment schedule appears broadly consistent with a Phase 3 metastatic pancreatic cancer trial, but travel and visit frequency may be greater than routine care, particularly for patients receiving chemotherapy and PK sampling.
Last updated: May 2026
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