Gemcitabine, Nab-paclitaxel, Durvalumab, and Oleclumab Before Surgery for the Treatment of in Resectable/Borderline Resectable Primary Pancreatic Cancer

Inclusion Criteria:

• Capable of giving written informed consent which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol. Written informed consent includes any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legalrepresentative prior to performing any protocol-related procedures, includingscreening evaluations

• Age >= 18 years at time of study entry

• Has histologically or cytologically confirmed resectable or borderline resectablepancreatic adenocarcinoma per MD Anderson criteria (borderline patients based uponreconstructable superior mesenteric vein/portal vein [SMV/PV] involvement orreconstructable hepatic artery involvement are allowed)

• Has received no prior anti-cancer therapy for pancreatic adenocarcinoma

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Hemoglobin >= 9.0 g/dL

• Absolute neutrophil count 1.5 x (>= 1500 per mm^3)

• Platelet count >=100 x 10^9/L (>= 100,000 per mm^3)

• Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). This will notapply to patients with confirmed Gilbert's syndrome (persistent or recurrenthyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis orhepatic pathology), who will be allowed only in consultation with their physician.Subjects requiring biliary decompression, biliary stent, or drainage usingpercutaneous trans-hepatic cholangiogram are allowed (patients with a decliningbilirubin status post stent placement are eligible with serum bilirubin =< 2.5 xinstitutional ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) /alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 xinstitutional ULN

• Measured creatinine clearance (CL) > 40 mL/min or calculated creatinine CL> 40mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urinecollection for determination of creatinine clearance

• Has evidence of post-menopausal status or negative urinary- or serum pregnancy testfor female, pre-menopausal patients. Women will be considered post-menopausal ifthey have been amenorrhoeic for 12 months without an alternative medical cause. Thefollowing age-specific requirements apply:

• Women < 50 years of age would be considered post-menopausal if they have beenamenorrhoeic for 12 months or more following cessation of exogenous hormonaltreatments and if they have luteinizing hormone and follicle-stimulatinghormone levels in the post-menopausal range for the institution or if theyunderwent surgical sterilization (bilateral oophorectomy or hysterectomy).

• Women >= 50 years of age would be considered post-menopausal if they have beenamenorrhoeic for 12 months or more following cessation of all exogenoushormonal treatments, had radiation-induced menopause with last menses >1 yearago, had chemotherapy-induced menopause with last menses > 1 year ago, orunderwent surgical sterilization (bilateral oophorectomy, bilateralsalpingectomy or hysterectomy)

• Is willing and able to comply with the protocol for the duration of the studyincluding undergoing treatment and scheduled visits and examinations includingfollow-up

• Must have a predicted life expectancy of at least 6 months

• Is willing to undergo mandatory research esophagogastroduodenoscopy/endoscopicultrasound for fine-needle aspiration (exceptions to this eligibility can bediscussed with principal investigator [PI] and will be considered on a case-by-casebasis)

• Has body weight of > 35 kg

Exclusion Criteria:

• Participated in another clinical study with an investigational product during thelast 4 weeks from the first dose of this study's treatment

• May need preoperative radiation therapy (as determined per the treating medicalteam: medical oncologist and/or surgical oncologist at time of study enrollment)

• Is concurrently enrolled in another clinical study (patient is eligible if the studyis an observational (non interventional) study or if enrollment is during thefollow-up period of an interventional study

• Has definitive evidence of metastatic disease per radiographic assessment

• Is receiving any concurrent chemotherapy, investigational product (IP), or biologic-or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy fornon-cancer-related conditions (e.g., hormone replacement therapy) is acceptable

• Had a major surgical procedure within 28 days prior to the first dose of IP (PORTplacement does not count; if classification is uncertain, discuss with PI)

• Has history of allogenic organ transplantation

• Has an active or previously documented autoimmune or inflammatory disorder (including inflammatory bowel disease [e.g., colitis or Crohn's disease],diverticulitis [diverticulosis is not an excluding factor], systemic lupuserythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis withpolyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).The following are exceptions to this criterion (and do not exclude patients fromparticipation):

• Patients with vitiligo or alopecia

• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable onhormone replacement

• Patients having any chronic skin condition that does not require systemictherapy

• Patients without active disease in the last 5 years (allowed only afterconsultation with the study physician)

• Patients with celiac disease controlled by diet alone

• Has uncontrolled intercurrent illness, including but not limited to, ongoing oractive infection; symptomatic congestive heart failure; uncontrolled hypertension;unstable angina pectoris; cardiac arrhythmia; interstitial lung disease; seriouschronic gastrointestinal conditions associated with diarrhea; or psychiatricillness/social situations that would limit compliance with study requirements, wouldsubstantially increase risk of incurring adverse events (AEs), or would compromisethe ability of the patient to give written informed consent

• Has a history of another primary malignancy. Patients having the following are stilleligible:

• Malignancy treated with curative intent, no known active disease >= 5 yearsbefore the first dose of IP, and low potential risk for recurrence

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidenceof disease

• Adequately treated carcinoma in situ without evidence of disease

• Has a history of leptomeningeal carcinomatosis

• Has a history of active primary immunodeficiency

• Has active infection including tuberculosis (clinical evaluation that includesclinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis Bvirus [HBV] surface antigen [HBsAg] result), or hepatitis C. Patients with a past orresolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (hepatitis C virus [HCV]) antibody are eligible only if polymerase chain reaction isnegative for HCV ribonucleic acid (RNA)

• Is currently using or previously used immunosuppressive medication within 14 daysbefore the first dose of durvalumab. The following medications are exceptions tothis criterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intraarticular injection)

• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day ofprednisone or its equivalent

• Steroids as premedication for hypersensitivity reactions (e.g., computedtomography [CT] scan premedication)

• Has received live attenuated vaccine within 30 days prior to the first dose of IP.Note: patients, if enrolled, should not receive live vaccine while receiving IP orduring the 30 days after the last dose of IP

• Is a female and pregnant or breastfeeding; or is a male or female of reproductivepotential who is not willing to employ effective birth control from time ofscreening to 90 days after the last dose of durvalumab and oleclumab monotherapy

• Has a known allergy or hypersensitivity to any of the study drugs or any of thestudy drug excipients

• Previously received clinical-trial treatment with durvalumab or oleclumab regardlessof treatment arm assignment

• Has laboratory evidence of hypercalcemia (>= 11 mg/dL [in presence of normalalbumin]) and/or hyperphosphatemia (>= 5.5 mg/dL)

• Has a history of venous thrombosis within the past 3 months prior to scheduled firstdose of study treatment and is not receiving fully dosed anticoagulation; or hassymptomatic venous thrombosis and symptoms have not improved

• Has a prior history of myocardial infarction, transient ischemic attack, or strokewithin the past 3 months prior to the scheduled first dose of study treatment

• Is unsuitable to participate in the study or is unlikely to comply with studyprocedures, restrictions and requirements (per judgment by the investigator)