Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )

NCT07621718 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: RMC-9805-305
• Study Type: interventional
• Target: 670
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with chemotherapy compared to placebo in combination with chemotherapy.

Conditions

Pancreatic Cancer; Pancreatic Cancer Metastatic; PDAC; PDAC - Pancreatic Ductal Adenocarcinoma; Pancreatic Ductal Adenocarcinoma (PDAC); Pancreatic Adenocarcinoma Metastatic; Pancreatic Adenocarcinoma; Pancreatic Adenosquamous Carcinoma

Keywords

Pancreatic Cancer; PDAC; Pancreatic Ductal Adenocarcinoma; RAS; KRAS; RAS Mutation; Pancreatic Cancer Metastatic; Pancreatic Adenocarcinoma Metastatic; Pancreatic Adenosquamous Carcinoma; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Progression free survival (PFS)

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

  Up to approximately 4 years

• Overall survival (OS)

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

  Up to approximately 4 years

Secondary Outcomes (9)

• PFS per blinded independent central review (BICR)

  Up to approximately 4 years

• Objective response rate (ORR)

  Up to approximately 4 years

• Duration of response (DOR)

  Up to approximately 4 years

• Incidence of adverse events (AEs)

  Up to approximately 4 years

• Changes in vital signs

  Up to approximately 4 years

Study Arms (2)

Arm A: zoldonrasib + chemotherapy

EXPERIMENTAL

study drug in combination with Investigator choice chemotherapy (mFFX or GnP)

Drug: Zoldonrasib; Drug: Oxaliplatin; Drug: Leucovorin (Calcium Folinate); Drug: 5-Fluorouracil; Drug: Irinotecan; Drug: Gemcitabine (GEM); Drug: Nab-paclitaxel

Arm B: placebo + chemotherapy

PLACEBO COMPARATOR

placebo in combination with Investigator choice chemotherapy (mFFX or GnP)

Drug: Placebo; Drug: Oxaliplatin; Drug: Leucovorin (Calcium Folinate); Drug: 5-Fluorouracil; Drug: Irinotecan; Drug: Gemcitabine (GEM); Drug: Nab-paclitaxel

Interventions

Zoldonrasib DRUG

oral tablets

Arm A: zoldonrasib + chemotherapy

Placebo DRUG

oral tablets

Arm B: placebo + chemotherapy

Oxaliplatin DRUG

IV infusion

Arm A: zoldonrasib + chemotherapy; Arm B: placebo + chemotherapy

Leucovorin (Calcium Folinate) DRUG

IV infusion

Arm A: zoldonrasib + chemotherapy; Arm B: placebo + chemotherapy

5-Fluorouracil DRUG

IV infusion

Arm A: zoldonrasib + chemotherapy; Arm B: placebo + chemotherapy

Irinotecan DRUG

IV infusion

Arm A: zoldonrasib + chemotherapy; Arm B: placebo + chemotherapy

Gemcitabine (GEM) DRUG

IV infusion

Arm A: zoldonrasib + chemotherapy; Arm B: placebo + chemotherapy

Nab-paclitaxel DRUG

IV infusion

Arm A: zoldonrasib + chemotherapy; Arm B: placebo + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Diagnosis of metastatic disease ≤ 6 weeks prior to screening.
• Documented KRAS G12D mutation status.
• Measurable disease per RECIST v1.1.
• Adequate organ function (bone marrow, liver, kidney, coagulation).
• Able to take oral medications.

You may not qualify if:

• Prior treatment with systemic anticancer therapy in unresectable locally advanced or metastatic setting.
• Prior systemic RAS-targeted therapy any time prior to randomization.
• Presence of other known driver mutations with approved targeted therapies
• Active or known history of untreated central nervous system metastatic 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.

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead

Study Sites (1)

Piedmont Healthcare

Atlanta, Georgia, 30318, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Oxaliplatin; Leucovorin; Fluorouracil; Irinotecan; Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids; Deoxycytidine; Cytidine; Pyrimidine Nucleosides

Central Study Contacts

Revolution Medicines Study Director

CONTACT

1-844-2-REVMED; medinfo@revmed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Chemotherapy administration will be open label. This study is double-blind with respect to zoldonrasib versus placebo and treatment assignments will remain blinded to the Investigator, study center staff, patient, Sponsor, and study vendors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2026
• First Posted: June 2, 2026
• Study Start: May 22, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): April 22, 2030
• Last Updated: June 2, 2026

Record last verified: 2026-05

Locations

US (1)