A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer
Start Date
2/17/2026
Completion Date
8/31/2029
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. 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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Setidegrasib
Oxaliplatin
Leucovorin
Irinotecan
fluorouracil
liposomal irinotecan
Placebo
Conditions
Locations
University of Arizona Cancer Center - North Campus
Tucson, Arizona 85719
United States
Mercy Cancer Center
Fort Smith, Arkansas 72903
United States
Crosson Cancer Institute at Providence St. Jude Medical Center in Fullerton
Fullerton, California 92835
United States
Cedars-Sinai - Cedars-Sinai Medical Center
Los Angeles, California 90048
United States
Hoag Mem Hosp Presbyterian
Newport Beach, California 92663
United States
Hartford Healthcare
Hartford, Connecticut 06016
United States
Baptist MD Anderson Cancer Institute
Jacksonville, Florida 32207
United States
Baptist Health Medical Group Oncology
Miami, Florida 33176
United States
Mount Sinai Medical Center - Miami Beach
Miami Beach, Florida 33140
United States
Indiana University Health - Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana 46202
United States
Saint Elizabeth Medical Center, Inc. DBA St. Elizabeth Health Care
Edgewood, Kentucky 41017
United States
University of Maryland School - Division of Hematology/Oncology
Baltimore, Maryland 21201
United States
University of Michigan Health - University of Michigan Medical Center
Ann Arbor, Michigan 48109
United States
Allina Health Cancer Institute - Hematology Cancer Care Services
Minneapolis, Minnesota 55407
United States
HealthPartners Frauenshuh Cancer Center
Saint Louis Park, Minnesota 55426
United States
HealthPartners Cancer Center at Regions Hospital
Saint Paul, Minnesota 55101
United States
Mercy CH Chub O'Reilly Cancer Center
Springfield, Missouri 65804
United States
The Alvin J. Siteman Cancer Center - Center for Advanced Med
St Louis, Missouri 63110
United States
Mercy David C. Pratt Cancer Center - St. - Mercy Research - David C. Pratt Cancer Center
St Louis, Missouri 63141
United States
Saint Joseph Hospital - Cancer Centers - St. Vincent Frontier Cancer Center
Billings, Montana 59102
United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire 03756
United States
Atlantic Health - Overlook Medical Center
Morristown, New Jersey 07962
United States
NYU Long Island Mineola
Mineola, New York 11501
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
United States
Memorial Sloan Kettering Cancer Center - Main Campus
New York, New York 10065
United States
University of Rochester
Rochester, New York 14611
United States
White Plains Hospital Center for Cancer Care - Oncology
White Plains, New York 10601
United States
Facilities Design and Construction - Energy Advancement and Innovation Center
Columbus, Ohio 43210
United States
Mercy Hospital Oklahoma City - Mercy Coletta Cancer Center - Oklahoma City
Oklahoma City, Oklahoma 73120
United States
AGH Singer Research Institute
Pittsburgh, Pennsylvania 15212
United States
Brown University Health Cancer Institute - Division of Hematology/Oncology
Providence, Rhode Island 02906
United States
UT Southwestern Medical Center at Dallas
Dallas, Texas 75390
United States
Houston Methodist Office of Graduate - Houston Methodist Neal Cancer Center at Texas Medical Center
Houston, Texas 77030
United States
Utah Cancer Specialists
Salt Lake City, Utah 84106
United States
UVA Emily Couric Cancer Center
Charlottesville, Virginia 22903
United States
Inova Schar Cancer Institute Clinical Trials
Fairfax, Virginia 22031
United States
Virginia Cancer Specialists
Fairfax, Virginia 22031
United States
Virginia Mason Franciscan Health - Virginia Mason Medical Center
Seattle, Washington 98101
United States
Fred Hutchinson Cancer Center - Advanced Cancer Research Group
Seattle, Washington 98109
United States
National Cancer Center Hospital East
Kashiwa, Chiba
Japan
Chugoku-Shikoku Group - Shikoku Cancer Center
Matsuyama, Ehime
Japan
Kyushu Group - Kyushu Cancer Center
Fukuoka, Fukuoka
Japan
Nara Medical University Hospital
Kashihara-shi, Nara
Japan
The University of Osaka Hospital
Suita, Osaka
Japan
The University of Tokyo Hospital
Bunkyo-ku, Tokyo
Japan
Japanese Foundation for Cancer Research - The Cancer Institute Hospital of JFCR
Koto, Tokyo
Japan
Yamaguchi University Hospital
Ube-shi, Yamaguchi
Japan
Osaka Prefectural Hospital Organization - Osaka International Cancer Institute
Osaka,
Japan