Tislelizumab and SX-682 before Surgery for the Treatment of Newly Diagnosed and Resectable Pancreatic Cancer

Inclusion Criteria

• Able to provide written informed consent and can understand and agree to comply with the requirements of the study and schedule of assessments
• Age ≥ 18 years on the day of signing the informed consent
• Have a newly diagnosed, biopsy-proven adenocarcinoma of the pancreas. If the biopsy is not sufficient for diagnosis, the patient can be considered to meet eligibility if the study team agrees that clinically the patient’s tumor is suspected to be adenocarcinoma
• Tumor must be deemed resectable by the study team prior to registration. Borderline resectable patients will be excluded
• Agree to undergo a core biopsy of the pancreatic tumor for both research and diagnosis purposes if a prior core biopsy was not performed or if archival tissue specimen is not available for the research purpose of this study
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• White blood cells (WBC) ≥ 2,000/μL
• Absolute neutrophil count (ANC) ≥ 1,500/μL
• Absolute blood lymphocyte count (ALC) ≥ 500/μL
• Platelets ≥ 100 x 10^3/µL
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.5 x ULN
• Amylase ≤ 2 x ULN
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG])
• Agree to follow contraception guidance, specifically: * Women of childbearing potential (WOCBP) must agree to use highly effective contraception for the duration of the study and for 4 months after last dose of study drug * Men who are sexually active with WOCBP must agree to use highly effective contraception for the duration of the study and for 6 months after last dose of study drug * Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception

Exclusion Criteria

• Have received any anti-pancreatic cancer therapy (symptomatic therapies are allowed), or any prior anti-cancer immunotherapy
• Have been diagnosed with another malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this study’s investigational drugs
• Any serious or uncontrolled medical or psychosocial disorder that could be exacerbated by the study treatment, impair the ability of the subject to comply with the study schedule, or interfere with interpretation of study results
• Active autoimmune disease or history of any autoimmune disease that may relapse. Patients with hypothyroidism managed with hormone replacement alone, vitiligo or psoriasis not requiring systemic treatment, and type I diabetes mellitus will be allowed
• Systemic steroid therapy (> 10mg daily prednisone equivalent) or immunosuppressive therapy within 14 days of first dose of study drug administration
• Active infection requiring systemic therapy
• Known history of human immunodeficiency virus (HIV)
• Active or chronic hepatitis B or hepatitis C (hepatitis c virus [HCV] antibody positive patients may be enrolled if they are confirmed with negative viral load at screening)
• History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, chronic obstructive pulmonary disease (COPD), asthma requiring medication, etc.
• Any of the following cardiovascular risk factors: * Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before first dose of study drug * Pulmonary embolism ≤ 28 days before first dose of study drug * Any acute myocardial infarction ≤ 6 months before first dose of study drug * Any history of heart failure meeting New York Heart Association (NYHA) Classification III or IV ≤ 6 months before first dose of study drug * Any event of ventricular arrhythmia ≥ grade 2 in severity ≤ 6 months before first dose of study drug * Any history of cerebrovascular accident ≤ 6 months before first dose of study drug * Uncontrolled hypertension: systolic ≥ 160 mmHg or diastolic ≥ 100 mmHg despiteanti-hypertension medications. Blood pressure may be rechecked as deemed appropriate by the investigator. If rechecked, patient must have two consecutive eligible readings to enroll * Any episode of syncope or seizure ≤ 28 days before first dose of study drug
• Prior allogeneic stem cell transplantation or organ transplantation
• Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drug
• Received a live vaccine ≤ 28 days before first dose of study drug (Vaccines for COVID-19 are allowed except for any live vaccine that may be developed. Seasonal flu vaccines are generally inactivated and are allowed. Intranasal vaccines are not allowed)
• Use of QT prolonging drugs within 2 weeks before the start of SX-682 dosing and for the length of the study
• Electrocardiogram (ECG) demonstrating a corrected QT (QTc) interval ≥ 470 msec or patients with congenital long QT syndrome
• History of severe hypersensitivity reaction to any monoclonal antibody
• Concurrent participation in another therapeutic clinical study
• Pregnant or breastfeeding