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Setidegrasib with mFOLFIRINOX or NALIRIFOX for KRAS G12D metastatic pancreatic cancer

A Phase 3, Double-blind, Placebo-controlled, Randomized Study to Assess the Efficacy and Safety of ASP3082 in Combination With mFOLFIRINOX or NALIRIFOX as First-line Treatment in Participants With KRAS G12D Mutated Metastatic Pancreatic Adenocarcinoma

Phase 3 Interventional Astellas Pharma Inc · NCT07409272

This trial tests whether adding setidegrasib to mFOLFIRINOX or NALIRIFOX helps people with metastatic pancreatic cancer who have a KRAS G12D mutation.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment614 (estimated)
Ages18 Years and up
SexAll
SponsorAstellas Pharma Inc Industry-sponsored
Drugs / interventionschemotherapy
Locations13 sites (Fullerton, California and 12 other locations)
Trial IDNCT07409272 on ClinicalTrials.gov

What this trial studies

This is a Phase 3 trial enrolling adults with metastatic pancreatic ductal adenocarcinoma and a confirmed KRAS G12D mutation to receive setidegrasib together with either mFOLFIRINOX or NALIRIFOX. Participants must have ECOG performance status 0–1, adequate organ function, and provide a baseline tumor tissue sample. The approach combines a targeted drug aimed at the abnormal KRAS G12D protein with standard multi-agent chemotherapy. Key outcomes include tumor response, progression-free and overall survival, and safety/tolerability.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed metastatic pancreatic ductal adenocarcinoma carrying a documented KRAS G12D mutation, ECOG 0–1, not eligible for curative surgery or radiotherapy, and with adequate organ function who can provide a tumor tissue sample.

Not a fit: People without the KRAS G12D mutation, with poor performance status (ECOG >1), inadequate organ function, or who cannot tolerate intensive chemotherapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, adding setidegrasib could slow tumor growth and extend survival for people with KRAS G12D metastatic pancreatic cancer.

How similar studies have performed: Targeting KRAS G12D is a relatively new approach: KRAS G12C inhibitors have shown benefit in other cancers, but clinical evidence for G12D-directed therapies remains limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Fullerton, California and 12 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Pancreatic CancerMetastatic Pancreatic CancerMetastatic Pancreatic AdenocarcinomaASP3082setidegrasibKRAS G12DPDACmFOLFIRINOX
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.