Canakinumab and Tislelizumab in Combination with Nab-Paclitaxel and Gemcitabine for the Treatment of Resectable Pancreatic Cancer

Inclusion Criteria

• Age >= 18 years at the time of informed consent
• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC) as determined by a local laboratory (adenosquamous is also allowed)
• Tumor confined to the pancreas and deemed resectable or borderline resectable per National Comprehensive Cancer Network (NCCN) guidelines for these criteria
• Patients must have not received previous anti-cancer therapy for the treatment of pancreatic ductal adenocarcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Absolute neutrophil count > 1500/mm^3 (obtained within the 21-day screening window)
• Platelets > 100,000/mm^3 (obtained within the 21-day screening window)
• Calculated creatinine clearance > 60 mL/min (Cockcroft Gault) (obtained within the 21-day screening window)
• Albumin > 3.0 g/dL (obtained within the 21-day screening window)
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) < 3.0 x upper limit of normal (ULN) (obtained within the 21-day screening window)
• Total bilirubin =< 1.5 X ULN (obtained within the 21-day screening window)
• Able to adhere to study visit schedule and other protocol requirements
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy
• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 9 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year * Highly effective contraception methods include: ** Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (i.e., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception ** Female sterilization (have had bilateral surgical oophorectomy [with or without hysterectomy], total hysterectomy or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment ** Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient ** Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception ** In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment ** Note: Women of non-childbearing potential is defined as women who are physiologically and/or anatomically incapable of becoming pregnant, as now further described: *** They are post-menopausal as evidenced by 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e., age appropriate history of vasomotor symptoms) *** They have had bilateral surgical oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks prior. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential **** Note: Sexually active male patients and their partners who are women of childbearing potential should follow the contraception recommendations and any other precautionary measures as required by the local prescribing information for the standard of care (SOC) anti-cancer

Exclusion Criteria

• Diagnosis of pancreatic neuroendocrine carcinoma or pancreatic acinar cell carcinoma
• Determined by the medical or surgical team to be a poor candidate for future surgical resection
• Has locally advanced or metastatic disease as determined by imaging * This includes those with a baseline cancer antigen (CA) 19-9 level > 1000 as these subjects have a high rate of metastatic disease
• Previous immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) for pancreatic cancer
• Known microsatellite instability-high (MSI-H) or mismatch repair-deficient pancreatic cancer
• Any prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1 inhibitor)
• Administration of a live vaccine within 30 days of the first dose of therapy on study
• History of known hypersensitivity to any of the drugs used in this study or any of their excipients, or patient has contraindication to any of the study drugs as outlined in the local prescribing information (e.g. United States Prescribing Information [USPI])
• Active autoimmune disease that has required systemic treatment in the past 2 years prior to enrollment i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs. Control of the disorder with replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted
• Patient has concurrent malignancy other than the disease under investigation, with exception of malignancy that was treated curatively and has not recurred within 2 years prior to the date of screening. Fully resected basal or squamous cell skin cancers, and any carcinoma in situ are eligible
• Subjects with a history of pneumonitis or interstitial lung disease requiring therapy
• Patient with suspected or proven immunocompromised state or infections, including: * Evidence of active or latent tuberculosis (TB) as determined by locally approved screening methods. If the results of the screening per local treatment guidelines or clinical practice require treatment, then the patient is not eligible * Known history of testing positive for human immunodeficiency virus (HIV) infections * Any other medical condition (such as active infection, treated or untreated), which in the opinion of the investigator places the patient at an unacceptable risk for participation in immunomodulatory therapy ** Note: Patients with localized condition unlikely to lead to a systemic infection e.g. chronic nail fungal infection are eligible
• Pre-existing peripheral neuropathy > grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] version [V] 5.0)
• Allogeneic bone marrow or solid organ transplant
• Uncontrolled or severe cardiac disease ([history of unstable angina, myocardial infarction, coronary stenting, or bypass surgery within the prior 6 months], symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia [including atrial flutter/fibrillation], requirement for inotropic support or use of devices for cardiac conditions [pacemakers/defibrillators]), uncontrolled hypertension defined by a systolic blood pressure => 160 mg and/or diastolic blood pressure >= 100 mg Hg
• Any significant medical condition, laboratory abnormality or psychiatric condition that would constitute unacceptable safety risks to the patients, contraindicate patient participation in the clinical study, limit the patient’s ability to comply with study requirements, or compromise patient’s compliance with the protocol and all requirements of the study as stated in the informed consent form