A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer

Summary

Pancreatic cancer is difficult to diagnose early. By the time people have been diagnosed, the cancer has usually spread to other parts of the body (metastatic). The standard treatment is chemotherapy, but other treatments are needed to improve outcomes in people with pancreatic cancer. The first treatment that people usually receive is chemotherapy. At the time this study started, some of the main standard chemotherapies for pancreatic cancer were mFOLFIRINOX or NALIRIFOX.

Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Many people with pancreatic cancer have a faulty KRAS gene. One such change in the KRAS gene is called a G12D mutation. Researchers are looking for ways to stop the actions of abnormal proteins made from the KRAS G12D mutation.

This study is about setidegrasib given with chemotherapy in people with pancreatic cancer who have the KRAS G12D mutation. Before setidegrasib can become an approved treatment, clinical studies need to be completed to understand how it works and how safe it is.

The main aim is to learn if people who are given setidegrasib with chemotherapy live for longer than people who are given placebo with chemotherapy. Other aims are to learn if setidegrasib delays the cancer and symptoms returning, how the body processes setidegrasib, and its safety, when given with chemotherapy.

People in this study will be adults with metastatic pancreatic cancer with the G12D mutation in their KRAS gene. Surgery or radiotherapy will not be an option to cure their cancer.

People cannot take part if the cancer cells have spread to the thin tissue covering the brain and spinal cord (leptomeningeal disease), have symptoms of cancer in the brain or nervous system, or have recently had some other cancers that required treatment.

In this study, people are given either setidegrasib with mFOLFIRINOX or NALIRIFOX chemotherapy, or a placebo with mFOLFIRINOX or NALIRIFOX chemotherapy. Whether people receive setidegrasib or placebo is decided by chance. The study doctor decides which chemotherapy (mFOLFIRINOX or NALIRIFOX) people receive. All of the study treatments are given slowly through a tube into a vein (infusion). People will continue to receive study treatment until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatment, they or the doctor decides the person should stop receiving study treatment, or sadly they pass away. There will be safety checks at each visit, and the doctors will continue to check for medical problems and people's wellbeing throughout the study.

Conditions

• Pancreatic Cancer
• Metastatic Pancreatic Cancer
• Metastatic Pancreatic Adenocarcinoma

Interventions

DRUG

Setidegrasib

Intravenous infusion

DRUG

Oxaliplatin

Intravenous infusion

DRUG

Leucovorin

Intravenous infusion

DRUG

Irinotecan

Intravenous infusion

DRUG

fluorouracil

Intravenous infusion

DRUG

liposomal irinotecan

Intravenous infusion

DRUG

Placebo

Intravenous Infusion

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.

  lead INDUSTRY

Principal Investigators

• Medical Director · Astellas Pharma Global Development, Inc.

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-17

Primary Completion

2029-08-31

Completion

2029-08-31

FDA Drug

Yes

Countries

• United States
• Japan

Study Locations