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 )

Revolution Medicines

Status and phase: Enrolling; Phase 3

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT07621718

RMC-9805-305

Details and patient eligibility

About

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.

Full description

This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with Investigator choice of chemotherapy will improve progression-free survival or overall survival compared to placebo in combination with Investigator choice of chemotherapy when given to patients with previously untreated, 1L metastatic KRAS G12D-mutated pancreatic adenocarcinoma. Choice of chemotherapy (mFFX or GnP) will be at the discretion of the Investigator.

Patients will be randomized to one of two arms: zoldonrasib + Investigator choice of chemotherapy (Arm A) or placebo + Investigator choice of chemotherapy (Arm B).

Enrollment: 670 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.
• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

670 participants in 2 patient groups, including a placebo group

Arm A: zoldonrasib + chemotherapy

Experimental group

Description:

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

Treatment:

Drug: Irinotecan

Drug: Zoldonrasib

Drug: Leucovorin (Calcium Folinate)

Drug: Oxaliplatin

Drug: Nab-paclitaxel

Drug: 5-Fluorouracil

Drug: Gemcitabine (GEM)

Arm B: placebo + chemotherapy

Placebo Comparator group

Description:

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

Treatment:

Drug: Irinotecan

Drug: Placebo

Drug: Leucovorin (Calcium Folinate)

Drug: Oxaliplatin

Drug: Nab-paclitaxel

Drug: 5-Fluorouracil

Drug: Gemcitabine (GEM)