A Phase 1B Study of Canakinumab, Spartalizumab, Nab-paclitaxel, and Gemcitabine in Metastatic Pancreatic Cancer (PC) Patients

Inclusion Criteria: * Age \> 18 years at the time of informed consent * Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC) (determined by a local laboratory) with metastatic spread of disease (adenosquamous is also allowed). * Patients must have not received previous anti-cancer therapy for the treatment of metastatic pancreatic ductal adenocarcinoma. * Patients who received previous neo-/adjuvant systemic therapy for non-metastatic PDAC ≥12 months from the last treatment to study enrollment date are allowed unless this therapy included immunotherapy and/or IL-1 inhibitors. * Radiographically measurable disease of at least one site by computed tomography (CT) scan (or magnetic resonance imaging, if allergic to CT contrast media) as defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Primary lesion is allowed as long as it is measurable (per RECIST 1.1) and has not been previously irradiated. Imaging results must be obtained within the 28-day screening window. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Adequate organ function (laboratory results must be obtained within the 28-day screening window) * Absolute neutrophil count \> 1500/mm3 * Hemoglobin \> 9 g/dL * Platelets \> 100,000/mm3 * Serum creatinine \< 1.5 x upper limit normal (ULN), or calculated creatinine clearance \> 60 mL/min (Cockcroft Gault) * Albumin \> 3.0 g/dL * Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) \< 3.0 x ULN (\< 5 x ULN in presence of liver metastasis). In patients with elevated ALT or AST, the values must be stable for at least 2 weeks and with no evidence of biliary obstruction on imaging * Total bilirubin ≤ 1.5 X ULN * INR ≤ 1.5 x ULN * Consent to provide protocol-mandated tissue and blood samples for diagnostic, PK, and research purposes * Able to adhere to study visit schedule and other protocol requirements Exclusion Criteria: * Diagnosis of pancreatic neuroendocrine carcinoma or pancreatic acinar cell carcinoma * 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). * Known microsatellite instability-high (MSI-H) or mismatch repair-deficient pancreatic cancer * Prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1 inhibitor). * 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 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. * Chronic or active hepatitis B or C * 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. * Allogeneic bone marrow or solid organ transplant * Treatment with any immune modulating agent in doses with systemic effects e.g.: * Systemic treatment with prednisone \> 10 mg (or equivalent) for \>14 days within 4 weeks prior to the first dose of study treatment. * Equivalent dose of methotrexate \> 15 mg weekly * Patient receiving any biologic drugs targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, or tocilizumab). * Note: Daily glucocorticoid-replacement for conditions such as adrenal or pituitary insufficiency is allowed. * Note: Topical, inhaled, or local steroid use in doses that are not considered to cause systemic effects are permitted (based on investigator's discretion and consultation with the Medical Monitor if needed). * 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. * 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 * Pre-existing peripheral neuropathy \> Grade 1 (CTCAE V 5.0) * Receipt of live vaccines within 3 months prior to the first dose of study treatment or while on active treatment within the trial (examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid (oral vaccine). Seasonal influenza vaccines for injection are generally killed virus vaccines and are permitted. However, intranasal influenza vaccines (e.g. Flu-mist) are live attenuated vaccines and are not permitted. * Patient has had major surgery within 14 days prior to enrollment * Patient has symptomatic brain metastases, or brain metastases that require directed therapy (such as focal radiotherapy or surgery). Patients with treated brain metastases have to be neurologically stable and not using systemic steroids for at least 4 weeks prior to the study drug administration. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are willing to use highly effective methods of contraception during treatment with study drugs (canakinumab, spartalizumab, gemcitabine and nab-paclitaxel). * Highly effective contraception methods are required while on treatment and for 150 days after stopping spartalizumab. No contraception is required after treatment with canakinumab is stopped. Contraception use after chemotherapy is stopped should be followed per the local drug label requirements. 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. * 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. Significant medical conditions include but are not limited to known history or current interstitial lung disease or non-infectious pneumonitis, medical history or current diagnosis of myocarditis, chronic active hepatitis, liver cirrhosis or any other significant liver disease with moderate to severe hepatic impairment (Child-Pugh B or C), serious non-healing wound/ulcer/bone fracture, uncompensated/symptomatic hypothyroidism, or requirement for hemodialysis or peritoneal dialysis. * Unwillingness or unable to comply with all requirement of the study as stated in the Informed Consent Form