ASP3082 in Combination With mFOLFIRINOX or NALIRIFOX in KRAS G12D-Mutated Metastatic Pancreatic Adenocarcinoma

What is the Purpose of this Study?

The purpose of this study is to evaluate the safety and effectiveness of an experimental drug called ASP3082 in people who have metastatic pancreatic ductal adenocarcinoma cancer (PDAC) with a KRAS G12D mutation when combined with chemotherapy and as compared to placebo combined with chemotherapy. The study will also examine how well an investigational test called QIAGEN Therascreen KRAS RCQ PCR assay can identify people who have PDAC with a KRAS G12D mutation to receive treatment with the study drug (ASP3082 and mFOLFIRINOX or NALIRIFOX). Study procedures include drug administration with ASP3082 or placebo with chemotherapy, physical examination, blood and urine labs, imaging scans, tumor biopsy, and questionnaires. Combination chemotherapy of FOLFIRINOX and NALIRIFOX are approved for patients with PDAC by the U.S. Food and Drug Adminsitration (FDA), but the combinations of ASP3082 with mFOLFIRINOX and NALIRIFOX are considered experimental.

Eligibility

* 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.

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.

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Where can I participate?

CS Cancer at Beverly Hills : Abrahm Levi
CS Cancer at Cedars-Sinai Medical Center : Abrahm Levi

More about this Clinical Trial

What is the full name of this clinical trial?

3082-CL-0301: 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

Study Details

Disease Type/Condition

Pancreas

Principal Investigator

Hendifar, Andrew

Co-Investigators

Andrew Horodner, Arsen Osipov, David Chan, Emily Kaymen, Hugo Hool, Jun Gong, Justin Wayne Tiulim, Syed Jilani, Thomas Lowe, Vanessa Dickey

Age Group

Adult

Phase

III

IRB Number

STUDY00004833

ClinicalTrials.gov ID

NCT07409272

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Abrahm Levi

Email

Abrahm.Levi@cshs.org