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

Conditions

• Metastatic Pancreatic Adenocarcinoma
• Metastatic Pancreatic Cancer
• Pancreatic Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Setidegrasib — DRUG
  Intravenous infusion
• Oxaliplatin — DRUG
  Intravenous infusion
• Leucovorin — DRUG
  Intravenous infusion
• Irinotecan — DRUG
  Intravenous infusion
• fluorouracil — DRUG
  Intravenous infusion
• liposomal irinotecan — DRUG
  Intravenous infusion
• Placebo — DRUG
  Intravenous Infusion

Study Details

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. People will only receive NALIRIFOX chemotherapy (with setidegrasib or placebo) after the safety of setidegrasib with NALIRIFOX chemotherapy has been confirmed in another ongoing setidegrasib study. 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.

Key Dates

First listed

Feb 13, 2026

Start date

Feb 17, 2026

Status verified

Jun 2026

Primary completion

Aug 31, 2029

Completion

Aug 31, 2029

Study Design

Enrollment

614 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Setidegrasib plus chemotherapy
  Participants will receive setidegrasib once weekly plus mFOLFIRINOX (oxaliplatin, leucovorin \[folinic acid or levofolinate\], irinotecan and 5-FU) or NALIRIFOX (liposomal irinotecan, oxaliplatin, leucovorin \[or levofolinate\] and 5 FU) chemotherapy on a 28-day cycle.
• Placebo Comparator: Placebo plus chemotherapy
  Participants will receive placebo once weekly plus mFOLFIRINOX (oxaliplatin, leucovorin \[folinic acid or levofolinate\], irinotecan and 5-FU) or NALIRIFOX (liposomal irinotecan, oxaliplatin, leucovorin \[or levofolinate\] and 5 FU) chemotherapy on a 28-day cycle.

Primary Outcome Measure

Overall Survival (OS) [ Time Frame: Up to 3.5 years ]

Central Contacts

• Astellas Pharma Global Development, Inc.
  800-888-7704
  [email protected]

Locations (28)

Find similar trials in Fort Smith, AR

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