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

NCT07409272 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 3082-CL-0301
• Study Type: interventional
• Target: 614
• Locations: 2 countries
• Sites: 17

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 ASP3082 or placebo) after the safety of ASP3082 with NALIRIFOX chemotherapy has been confirmed in another ongoing ASP3082 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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS is defined as the time from the date of randomization until the date of death from any cause.

  Up to 3.5 years

Secondary Outcomes (17)

• Progression-Free Survival (PFS) per RECIST v1.1. as assessed by the investigator.

  Up to 3.5 years

• Time to Improvement in Pancreatic Pain (TIPP) measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-PAN26).

  Up to 3.5 years

• Time to Worsening of General Health Status/Quality of Life (GHS/QoL) (TWGQ) measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

  Up to 3.5 years

• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1,

  Up to 3.5 years

• Number of Participants with Adverse Events (AEs)

  Up to 3.5 years

Study Arms (2)

Setidegrasib plus chemotherapy

EXPERIMENTAL

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.

Drug: Setidegrasib; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: fluorouracil; Drug: liposomal irinotecan

Placebo plus chemotherapy

PLACEBO COMPARATOR

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.

Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: fluorouracil; Drug: liposomal irinotecan; Drug: Placebo

Interventions

Leucovorin DRUG

Intravenous infusion

Also known as: folinic acid, levofolinate

Placebo plus chemotherapy; Setidegrasib plus chemotherapy

Irinotecan DRUG

Intravenous infusion

Placebo plus chemotherapy; Setidegrasib plus chemotherapy

Setidegrasib DRUG

Intravenous infusion

Also known as: ASP3082

Setidegrasib plus chemotherapy

Oxaliplatin DRUG

Intravenous infusion

Placebo plus chemotherapy; Setidegrasib plus chemotherapy

fluorouracil DRUG

Intravenous infusion

Also known as: 5-FU

Placebo plus chemotherapy; Setidegrasib plus chemotherapy

liposomal irinotecan DRUG

Intravenous infusion

Placebo plus chemotherapy; Setidegrasib plus chemotherapy

Placebo DRUG

Intravenous Infusion

Placebo plus chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (17)

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

Fullerton, California, 92835, United States

RECRUITING

Hoag Mem Hosp Presbyterian

Newport Beach, California, 92663, United States

RECRUITING

Baptist MD Anderson Cancer Institute

Jacksonville, Florida, 32207, United States

RECRUITING

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

Edgewood, Kentucky, 41017, United States

RECRUITING

HealthPartners Frauenshuh Cancer Center

Saint Louis Park, Minnesota, 55426, United States

RECRUITING

HealthPartners Cancer Center at Regions Hospital

Saint Paul, Minnesota, 55101, United States

RECRUITING

NYU Long Island Mineola

Mineola, New York, 11501, United States

RECRUITING

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

RECRUITING

White Plains Hospital Center for Cancer Care - Oncology

White Plains, New York, 10601, United States

RECRUITING

UT Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

RECRUITING

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

RECRUITING

UVA Emily Couric Cancer Center

Charlottesville, Virginia, 22903, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Mason Franciscan Health - Virginia Mason Medical Center

Seattle, Washington, 98101, United States

RECRUITING

Kyushu Group - Kyushu Cancer Center

Fukuoka, Fukuoka, Japan

RECRUITING

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, Japan

RECRUITING

Yamaguchi University Hospital

Ube-shi, Yamaguchi, Japan

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Oxaliplatin; Leucovorin; Irinotecan; Fluorouracil; irinotecan sucrosofate

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Central Study Contacts

Astellas Pharma Global Development, Inc.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 13, 2026
• Study Start: February 17, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

US (14); JP (3)