Recruiting
Phase 3

Setidegrasib with Chemotherapy

Sponsor:

Astellas Pharma Global Development, Inc.

Code:

NCT07409272

Conditions

Pancreatic Cancer

Metastatic Pancreatic Cancer

Metastatic Pancreatic Adenocarcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Setidegrasib

Oxaliplatin

Leucovorin

Irinotecan

fluorouracil

Study Details

Brief 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.

Conditions

Pancreatic Cancer

Metastatic Pancreatic Cancer

Metastatic Pancreatic Adenocarcinoma

Study ID

NCT07409272

Start date

Feb 17, 2026

Status verified date

Aug, 2026

Completion date

Aug 31, 2029

Anticipated

Primary completion date

Aug 31, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Participant has histologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) with documented Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutation based on local or central testing (confirmation of a participant's positive KRAS G12D mutation result must be available prior to randomization).
  • Participant has no option for surgical resection or radiotherapy with curative intent.
  • Participant consents to and provides a baseline tumor tissue specimen for the study during screening. The sample must meet the requirements described in the laboratory manual and the tumor sample guidance.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 within 7 days prior to randomization.
  • Participant has adequate organ function as indicated by the following laboratory values within 7 days prior to randomization (if a participant has received a recent blood transfusion, the latest laboratory tests must be obtained ≥ 14 days after any blood transfusion). The laboratory values prior to the initiation of the first dose of setidegrasib/placebo (or mFOLFIRINOX/NALIRIFOX, if chemotherapy is administered during the screening period) should be used to determine eligibility. Participants who receive mFOLFIRINOX/NALIRIFOX during the screening period must meet these criteria within 7 days prior to the start of on-treatment chemotherapy (i.e., C1D1).
  • Participant agrees not to participate in another interventional study while receiving study intervention in the present study (participant who is currently in the follow-up period of an interventional clinical trial is allowed).

Exclusion Criteria:

  • Participant has neuroendocrine, acinar pancreatic carcinoma or pancreatic cancer with squamous/adenosquamous features.
  • Participant has another prior malignancy active (i.e., requiring treatment, including hormonal therapies, or intervention) within the previous 2 years different from the primary malignancy for this study, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed.
  • Participant has chronic inflammatory bowel disease, bowel obstruction and/or severe uncontrolled diarrhea.
  • Participant has peripheral sensory neuropathy with functional impairment.
  • Participant has ascites and/or pleural effusion that require invasive interventions within 30 days prior to randomization or have an indwelling drainage catheter.
  • Participant has symptomatic pulmonary embolism or pulmonary embolism not being treated with anticoagulation.
  • Participant has a history of interstitial lung disease or pulmonary fibrosis.
  • Participant has uncontrolled seizure disorder or refractory to antiepileptics.
  • Participant has known homozygous uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism.
  • Participant has had a myocardial infarction, unstable angina or coronary artery bypass surgery within 6 months prior to randomization or currently has an uncontrolled illness including but not limited to symptomatic congestive heart failure, clinically significant cardiac disease (e.g., cardiomyopathy, infiltrative cardiac disease, etc.), unstable angina pectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker or long QT interval (QT) syndrome.
  • Participant has received any prior systemic therapy for their metastatic PDAC (except with up to 2 doses \[i.e., 28 days; 1 cycle\] of mFOLFIRINOX or NALIRIFOX during the screening period. If a participant received \[neo\]adjuvant chemotherapy, tumor recurrence or disease progression must have occurred ≥ 6 months after completing the last dose of the \[neo\]adjuvant therapy).
  • Participant has had prior treatment with a KRAS G12D-targeted agent.
  • Participant has a corrected QT interval by Fridericia (QTcF) (single electrocardiogram \[ECG\]) > 470 msec during the screening period.

Study Design

Enrollment

614 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

Setidegrasib

Intravenous infusion

Oxaliplatin

Intravenous infusion

Leucovorin

Intravenous infusion

Irinotecan

Intravenous infusion

fluorouracil

Intravenous infusion

liposomal irinotecan

Intravenous infusion

Placebo

Intravenous Infusion

Primary outcome measure

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

Central Contacts and Locations

Central contacts

Astellas Pharma Global Development, Inc.

800-888-7704Astellas.registration@astellas.com

Locations

University of Arizona Cancer Center - North Campus

Recruiting

Tucson, Arizona, United States, 85719

Mercy Cancer Center

Recruiting

Fort Smith, Arkansas, United States, 72903

Crosson Cancer Institute at Providence St. Jude Medical Center in Fullerton

Recruiting

Fullerton, California, United States, 92835

UCI Health - Irvine

Recruiting

Irvine, California, United States, 92612

Cedars-Sinai - Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Hoag Mem Hosp Presbyterian

Recruiting

Newport Beach, California, United States, 92663

UC Irvine Health-Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868-3201

Hartford Healthcare

Recruiting

Hartford, Connecticut, United States, 06016

Baptist MD Anderson Cancer Institute

Recruiting

Jacksonville, Florida, United States, 32207

Baptist Health Medical Group Oncology

Recruiting

Miami, Florida, United States, 33176

Mount Sinai Medical Center - Miami Beach

Recruiting

Miami Beach, Florida, United States, 33140

Piedmont Healthcare - Piedmont Physicians Medical Oncology Atlanta

Recruiting

Atlanta, Georgia, United States, 30318

Indiana University Health - Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Recruiting

Indianapolis, Indiana, United States, 46202

Saint Elizabeth Medical Center, Inc. DBA St. Elizabeth Health Care

Recruiting

Edgewood, Kentucky, United States, 41017

University of Maryland School - Division of Hematology/Oncology

Recruiting

Baltimore, Maryland, United States, 21201

University of Michigan Health - University of Michigan Medical Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Allina Health Cancer Institute - Hematology Cancer Care Services

Recruiting

Minneapolis, Minnesota, United States, 55407

HealthPartners Frauenshuh Cancer Center

Recruiting

Saint Louis Park, Minnesota, United States, 55426

HealthPartners Cancer Center at Regions Hospital

Recruiting

Saint Paul, Minnesota, United States, 55101

Mercy CH Chub O'Reilly Cancer Center

Recruiting

Springfield, Missouri, United States, 65804

The Alvin J. Siteman Cancer Center - Center for Advanced Med

Recruiting

St Louis, Missouri, United States, 63110

Mercy David C. Pratt Cancer Center - St. - Mercy Research - David C. Pratt Cancer Center

Recruiting

St Louis, Missouri, United States, 63141

Saint Joseph Hospital - Cancer Centers - St. Vincent Frontier Cancer Center

Recruiting

Billings, Montana, United States, 59102

Dartmouth Hitchcock Medical Center

Recruiting

Lebanon, New Hampshire, United States, 03756

Memorial Sloan Kettering - Hackensack - Memorial Sloan Kettering Basking Ridge

Recruiting

Basking Ridge, New Jersey, United States, 07920

Memorial Sloan Kettering Cancer Center - Monmouth

Recruiting

Middletown, New Jersey, United States, 00748-3052

Memorial Sloan Kettering Bergen

Recruiting

Montvale, New Jersey, United States, 07645

Atlantic Health - Overlook Medical Center

Recruiting

Morristown, New Jersey, United States, 07962

Roswell Park Comprehensive Cancer Center

Recruiting

Buffalo, New York, United States, 14263

Memorial Sloan Kettering Commack

Recruiting

Commack, New York, United States, 11725

Memorial Sloan Kettering Westchester

Recruiting

Harrison, New York, United States, 10604

NYU Long Island Mineola

Recruiting

Mineola, New York, United States, 11501

Laura and Isaac Perlmutter Cancer Center at NYU Langone

Recruiting

New York, New York, United States, 10016

Memorial Sloan Kettering Cancer Center - Main Campus

Recruiting

New York, New York, United States, 10065

University of Rochester

Recruiting

Rochester, New York, United States, 14611

Memorial Sloan Kettering Nassau

Recruiting

Uniondale, New York, United States, 11553

White Plains Hospital Center for Cancer Care - Oncology

Recruiting

White Plains, New York, United States, 10601

Facilities Design and Construction - Energy Advancement and Innovation Center

Recruiting

Columbus, Ohio, United States, 43210

Mercy Hospital Oklahoma City - Mercy Coletta Cancer Center - Oklahoma City

Recruiting

Oklahoma City, Oklahoma, United States, 73120

Oregon Health & Science University - OHSU Knight Cancer Institute

Recruiting

Portland, Oregon, United States, 97201

AGH Singer Research Institute

Recruiting

Pittsburgh, Pennsylvania, United States, 15212

Brown University Health Cancer Institute - Division of Hematology/Oncology

Recruiting

Providence, Rhode Island, United States, 02906

UT Southwestern Medical Center at Dallas

Recruiting

Dallas, Texas, United States, 75390

Houston Methodist Office of Graduate - Houston Methodist Neal Cancer Center at Texas Medical Center

Recruiting

Houston, Texas, United States, 77030

Utah Cancer Specialists

Recruiting

Salt Lake City, Utah, United States, 84106

UVA Emily Couric Cancer Center

Recruiting

Charlottesville, Virginia, United States, 22903

Inova Schar Cancer Institute Clinical Trials

Recruiting

Fairfax, Virginia, United States, 22031

Virginia Mason Franciscan Health - Virginia Mason Medical Center

Recruiting

Seattle, Washington, United States, 98101

Fred Hutchinson Cancer Center - Advanced Cancer Research Group

Recruiting

Seattle, Washington, United States, 98109

More Information

Sponsor

Astellas Pharma Global Development, Inc.

Last update posted

Aug 27, 2026

Last verified

Aug, 2026

Keywords

  • Pancreatic Cancer
  • Metastatic Pancreatic Cancer
  • Metastatic Pancreatic Adenocarcinoma
  • ASP3082
  • setidegrasib
  • KRAS G12D
  • PDAC
  • mFOLFIRINOX
  • NALIRIFOX

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Astellas Pharma Global Development, Inc. on 2026-08-27.