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NCT Number: NCT07805954

Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma

The purpose of this study is to evaluate the efficacy of combination therapy with two investigational RAS(ON) inhibitors (daraxonrasib and zoldonrasib) compared to chemotherapy.

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Key information

Conditions

Pancreatic Cancer Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Neoplasms Neoplasms by Site PDAC PDAC - Pancreatic Ductal Adenocarcinoma Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma Metastatic Pancreatic Adenosquamous Carcinoma Pancreatic Cancer Metastatic Pancreatic Diseases Pancreatic Ductal Adenocarcinoma (PDAC) Pancreatic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location status: Recruiting

Location contact

Cheyenne Schneider

CONTACT

[email protected]

813-745-5166

About this study

This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib plus zoldonrasib will improve progression-free survival and/or overall survival compared with standard gemcitabine and nab-paclitaxel when given as first-line treatment in patients with metastatic KRAS G12D-mutated pancreatic adenocarcinoma.

Patients will be randomized to one of two arms: daraxonrasib + zoldonrasib (Arm A) or gemcitabine and nab-paclitaxel (Arm B).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • At least 18 years old and has provided informed consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Histologically or cytologically confirmed pancreatic adenocarcinoma, including adenosquamous carcinoma, not previously treated in the locally advanced unresectable or metastatic setting.
  • No prior treatment in the locally advanced unresectable or metastatic setting
  • Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent.
  • Documented KRAS G12D mutation status.
  • Measurable disease per RECIST v1.1.
  • Adequate organ function (bone marrow, liver, kidney, coagulation).

Exclusion criteria

  • Mutation status with known driver mutations for which there are approved targeted therapies.
  • Acinar cell carcinoma, pancreatic neuroendocrine tumors, tumors involving islet cells or islet cell neoplasms, and other non-adenocarcinoma pancreatic malignancies.
  • Tumors determined to originate from non-pancreatic primary sites.
  • Prior treatment with MAPK-pathway targeted therapy or administration of RAS-targeted vaccine in the metastatic setting.
  • Active or known history of untreated central nervous system metastatic or leptomeningeal disease.
  • Any conditions that may affect the ability to take or absorb study drug.
  • Major surgery within 28 days prior to randomization.
  • Patient is unable or unwilling to comply with protocol-required study visits or procedures.
  • Additional inclusion & exclusion criteria may apply.

Treatment and study plan

daraxonrasib

Drug

oral tablets

Gemcitabine

Drug

intravenous (IV) infusion

Nab-paclitaxel

Drug

IV infusion

Zoldonrasib

Drug

oral tablets

Primary outcomes

  1. Progression free survival (PFS)

    Time frame: Up to approximately 4 years

    PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per response evaluation criteria in solid tumors (RECIST) v1.1 and as assessed by Investigator.

  2. Overall survival (OS)

    Time frame: Up to approximately 4 years

    OS is defined as the time from randomization until death from any cause.

Secondary outcomes

  1. PFS by blinded independent central review (BICR)

    Time frame: Up to approximately 4 years

    PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is assessed per RECIST v1.1 by BICR

  2. Objective response rate (ORR)

    Time frame: Up to approximately 4 years

    Objective response is defined as partial response (PR) or complete response (CR) per RECIST v1.1, as assessed by the Investigator.

  3. Duration of response (DOR)

    Time frame: Up to approximately 4 years

    DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first, as assessed by the investigator.

  4. Incidence of adverse events (AEs)

    Time frame: Up to approximately 4 years

    Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5

  5. Changes in vital signs

    Time frame: Up to approximately 4 years

    Number of patients with changes from baseline in vital signs

  6. Changes in clinical laboratory test values

    Time frame: Up to approximately 4 years

    Number of patients with changes from baseline in clinical laboratory test values

  7. Concentration of daraxonrasib and zoldonrasib in Arm A

    Time frame: Up to Cycle 5 Day 1 (each cycle is 28 days)

    Pre-dose trough and post-dose blood concentrations of daraxonrasib and zoldonrasib at selected visits.

  8. Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) pain scale

    Time frame: Up to approximately 4 years

    EORTC QLQ-PAN26 consists of 26 questions relating to disease symptoms, treatment side effects and emotional issues specific to pancreatic cancer. The pancreatic pain subscale assesses abdominal pain, back pain, and pain while lying down. Change in score from baseline in the pain subscale will be assessed with higher scores on the pain subscale indicating more severe pain and worsening function.

  9. Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status score

    Time frame: Up to approximately 4 years

    EORTC QLQ-C30 consists of 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties), and an overall scale for global health status. It uses a mix of 4-point scales and 7-point scales. Change from baseline in EORTC QLQ-C30 global health status will be assessed. Higher scores on functional scales reflect better functioning, whereas higher scores on symptom scales reflect higher symptom burden.

Study contacts

Contact information is provided by the study sponsor or research team.

Revolution Medicines Study Director

CONTACT

[email protected]

1-844-2-REVMED

Sponsors and collaborators

Lead sponsor

Revolution Medicines, Inc.

Industry

Registry information

Official study title

A Phase 3, Randomized, Open-Label Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Patients With Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma

Acronym: RASolute 309

Important dates

Study start
2026
Primary completion
2029
Study completion
2030
First posted
Sep 8, 2026
Registry last updated
Sep 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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