A Study of ASP2138 Given Before Surgery, Then Chemotherapy After Surgery, in People With Pancreatic Ductal Cancer

Inclusion Criteria:

• Participant has histologically confirmed localized pancreatic adenocarcinoma whichis deemed upfront resectable based on institutional multi-disciplinary review.Participant with localized pancreatic adenocarcinoma cannot have received any priortherapy.

• Participant has confirmation of positive claudin (CLDN)18.2 test result by locallaboratory prior to first dose of study intervention (ASP2138 dosing may be allowedafter discussion with the medical monitor, if results are pending or a biopsy forCLDN18.2 testing is not clinically appropriate). Site should contact the sponsor toassess potential eligibility based on a local test result.

• Participant has an available pretreatment tumor sample, if clinically appropriateand meets requirements.

• Participant is able to undergo surgery and treatment with adjuvant chemotherapy perinstitutional standard of care.

• Participant with a known history or current symptoms of cardiac disease, or historyof treatment with cardiotoxic agents, should have a clinical risk assessment ofcardiac function of class 2B or better using the New York Heart AssociationFunctional Classification.

• Female participant is not pregnant and at least 1 of the following conditions apply:

• Not a woman of childbearing potential (WOCBP)

• WOCBP who has a negative serum pregnancy test at screening and agrees to followthe contraceptive guidance from the time of informed consent through at least 6months after final ASP2138 intervention administration (or follow thecontraception requirements per the adjuvant chemotherapy package insert [PI]/prescribing information, whichever is longer).

• Female participant must not be breastfeeding or lactating starting at screening andthroughout the investigational period and for 5 half-lives (6 months) after finalASP2138 intervention administration (or follow the contraception requirements perthe adjuvant chemotherapy PI/prescribing information, whichever is longer).

• Female participant must not donate ova starting at first administration ofneoadjuvant ASP2138, throughout the investigational period, and for 6 months afterfinal ASP2138 administration (or follow the contraception requirements per theadjuvant chemotherapy PI/prescribing information, whichever is longer).

• Male participant must agree to use contraception with female partner(s) ofchildbearing potential (including breastfeeding partner) throughout the treatmentperiod and for 6 months after final ASP2138 intervention administration (or followthe contraception requirements per the adjuvant chemotherapy PI/prescribinginformation, whichever is longer).

• Male participant must agree to remain abstinent or use a condom with pregnantpartner(s) for the duration of the pregnancy throughout the investigational periodand for 6 months after final ASP2138 intervention administration (or follow thecontraception requirements per the adjuvant chemotherapy PI/prescribing information,whichever is longer).

• Male participant must not donate sperm during the treatment period and for 6 monthsafter ASP2138 intervention administration (or follow the contraception requirementsper the adjuvant chemotherapy PI/prescribing information, whichever is longer).

• Participant has at least 1 measurable lesion according to Response EvaluationCriteria in Solid Tumors (RECIST) v1.1 within 28 days prior to the first dose ofstudy intervention per investigator assessment.

• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0or 1.

• Participant has a corrected QT interval by Fridericia (QTcF) ≤ 470 msec.

• Participant must meet all of the criteria based on laboratory tests within 7 daysprior to the first dose of study intervention. Participant has adequate organ andmarrow function. If a participant has received a recent blood transfusion, thelaboratory tests must be obtained ≥ 1 week after any blood transfusion.

• Participant agrees not to participate in another interventional study whilereceiving study intervention in the present study.

Exclusion Criteria:

• Participant has had within 6 months prior to first dose of study intervention any ofthe following: unstable angina, myocardial infarction, ventricular arrhythmiarequiring intervention or hospitalization for heart failure.

• Participant has active infection requiring systemic therapy that has not completelyresolved within 7 days prior to the start of study intervention.

• Participant has active autoimmune disease that has required systemicimmunosuppressive treatment within the past 1 month prior to the start of studyintervention.

• Participant has uncontrolled serious psychiatric illness or social situations thatwould preclude study compliance.

• Participant has another malignancy for which treatment is required.

• Participant has a history or complication of interstitial lung disease.

• Participant has a complete gastric outlet syndrome or a partial gastric outletsyndrome with persistent/recurrent vomiting.

• Participant has known dihydropyrimidine dehydrogenase (DPD) deficiency. NOTE:Applicable if participant is receiving fluoropyrimidine containing chemotherapy.Screening for DPD deficiency should be conducted per local requirements.

• Participant has known, existing uncontrolled coagulopathy. Concomitant treatmentwith full dose warfarin (coumadin) is not allowed.

• Participant may receive low molecular weight heparin (LMWH) (such as enoxaparinand dalteparin) and direct oral anticoagulant (DOAC) for management of deepvenous thrombosis (DVT).

• Participant has a history of bleeding diathesis or recent major bleeding events (i.e. Grade ≥ 2 bleeding events in the month prior to treatment).

• Participant has uncontrolled intercurrent illness or infection.

• Participant is known to have human immunodeficiency virus (HIV) infection. However,participants with cluster of differentiation (CD) 4+ T cell counts ≥ 350 cells/µLand no history of acquired immunodeficiency syndrome (AIDS) defining opportunisticinfections within the past 6 months are eligible. NOTE: Screening for HIV infectionshould be conducted per local requirements.

• Participant is known to have active hepatitis B (positive hepatitis B surfaceantigen [hBsAg]) or hepatitis C infection. Testing is required for known history ofthese infections or as mandated by local requirements. NOTE: Screening for theseinfections should be conducted per local requirements.

• For participant who is negative for hBsAg, but hepatitis B core (HBc) Abpositive, an HBV DNA test will be performed and if positive the participantwill be excluded.

• Participant with positive hepatitis C virus (HCV) serology, but negative HCVRNA test results is eligible.

• Participant treated for HCV with undetectable viral load results is eligible.

• Participant has a known history of UGT1A1 gene polymorphism resulting in completeloss of function of the UGT1A1 gene product (for participants receiving irinotecancontaining chemotherapy).

• Participant has any pre-existing severe gastric conditions such as active gastritisor ulcer that could be exacerbated by treatment.

• Participant has received any prior chemotherapy, radiation therapy, immunotherapy,or biologic ("targeted") therapy or investigational therapy for treatment of theparticipant's pancreatic tumor.

• Participant has received a live vaccine within 30 days of planned start of studytherapy. NOTE: Seasonal influenza vaccines for injection are generally inactivatedflu vaccines and are allowed.

• Participant has any condition including clinically significant disease orco-morbidity that may adversely affect the safe delivery of treatment within thisstudy or make the participant unsuitable for study participation.

• Participant has prior severe allergic reaction; suspected, known immediate ordelayed hypersensitivity; or intolerance or contraindication to any studyintervention.

• Participant has had a major surgical procedure 28 days before start of studyintervention and has not fully recovered.