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 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) 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