Phase 3 Study of Adjuvant Daraxonrasib Versus Observation in Patients With Resected Pancreatic Ductal Adenocarcinoma Following Neoadjuvant or Adjuvant Chemotherapy

The primary objective of this study is to compare the treatment effect of daraxonrasib versus standard of care observation in patients with resected pancreatic ductal adenocarcinoma following the completion of neoadjuvant and/or adjuvant chemotherapy. 5: Efficacy.

The secondary objectives include:

• Comparison of overall survival between the daraxonrasib and observation groups.
• Evaluation of disease-free survival as assessed by blinded independent central review.
• Assessment of the disease-free survival rate at 1 and 2 years.
• Comparison of the overall survival rate at 1 and 2 years.
• Evaluation of the safety and tolerability of daraxonrasib. 4: Safety.
• Characterization of the pharmacokinetics of daraxonrasib. 6: Pharmacokinetic.

This clinical trial involves a total of 402 participants diagnosed with resected pancreatic ductal adenocarcinoma. The study population includes both male and female individuals within specified age cohorts. Eligible participants must have a histologically confirmed diagnosis following successful surgical resection with no evidence of recurrent or metastatic disease. A requirement for inclusion is the prior administration of perioperative chemotherapy, with the most recent treatment completed within the previous 12 weeks. Participants are required to have a documented RAS mutation status and an Eastern Cooperative Oncology Group performance status of 0 or 1. Additionally, subjects must demonstrate adequate organ function involving the bone marrow, liver, kidneys, and coagulation systems.

This Phase 3, multicenter, open-label, randomized, 2-arm study evaluates the efficacy, safety, and pharmacokinetics of daraxonrasib compared to standard of care observation. The trial is designed for patients with resected pancreatic ductal adenocarcinoma who have completed neoadjuvant and/or adjuvant chemotherapy. Participants are assigned to receive either 300 mg of daraxonrasib administered orally or undergo clinical observation. The primary endpoint is disease-free survival, while secondary endpoints include overall survival, disease-free survival rates at one and two years, and the assessment of safety and tolerability. The study period is estimated to conclude by July 2030. Clinical assessment includes a screening process to confirm histologically confirmed disease status, RAS mutation status, and adequate organ function, followed by necessary follow-up evaluations to monitor disease recurrence or mortality.

Daraxonrasib (RMC-6236) is an experimental medication administered as a tablet. The dosage is 300 mg, which is delivered via oral use.

The comparator treatment consists of standard of care observation following the completion of neoadjuvant and/or adjuvant chemotherapy for patients with resected pancreatic ductal adenocarcinoma.

The primary efficacy endpoint is disease-free survival (DFS) as determined by the investigator. DFS is defined as the duration from randomization until disease recurrence or death from any cause. Recurrence is evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary efficacy endpoints include:

• Overall survival (OS), defined as the time from randomization until death from any cause.
• DFS as assessed by blinded independent central review (BICR) using RECIST v1.1.
• The DFS rate at 1 year and 2 years.
• The OS rate at 1 year and 2 years.