Siltuximab and Spartalizumab in Patients With Metastatic Pancreatic Cancer

Inclusion Criteria: * Cytological or histologic diagnosis and metastatic pancreatic adenocarcinoma disease that has failed at least one standard regimen such as gemcitabine nab-paclitaxel or folinic acid, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX). * Patient must meet the following laboratory values at the screening visit: * Absolute neutrophil count ≥ 1.5 x 109/L * Platelets ≥ 75 x 109/L * Hemoglobin (Hgb) ≥ 9 g/dL * Serum creatinine \< 1.5 mg/dL OR Creatinine Clearance ≥ 45 mL/min using Cockcroft-Gault formula * Total bilirubin ≤ 1.5 x ULN * Aspartate transaminase (AST) ≤ 2.5 x ULN, except for patients with liver metastasis, who may only be included if AST ≤ 5.0 x upper limit of normal (ULN) * Alanine transaminase (ALT) ≤ 2.5 x ULN, except for patients with liver metastasis, who may only be included if ALT ≤ 5.0 x ULN * Presence of measurable disease by RECIST criteria * Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Written informed consent must be obtained prior to any screening procedures. * Normal ECG defined as the following: * Resting heart rate 50-90 bpm * QT corrected for HR using Fridericia's method (QTcF) at screening \< 450 ms (male patients), \< 460 ms (female patients) * Before enrollment, a woman must be either: * Not of childbearing potential: postmenopausal (\> 45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level \> 40 IU/mL); permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy * Of childbearing potential and practicing (during the study and for 150 days after receiving the last dose of study agent) a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: eg, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject) * Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active) a woman must begin a highly effective method of birth control, as described above. * A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin \[β-hCG\]) or urine pregnancy test at screening. * During the study and for 150 days after receiving the last dose of study agent, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction. * A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug. * Sign an informed consent document indicating that they understand the purpose of and procedures required for the study, are willing to participate in the study, and are willing and able to adhere to the prohibitions and restrictions specified in this protocol. Informed consent must be obtained before performing any study specific procedures. Exclusion Criteria: * Prior exposure to agents targeting programmed cell death protein-1 (PD-1), PD-L1, IL-6 or the IL-6 receptor. Prior chemotherapy is allowed as long as adequate washout period of ≥ 4 weeks. * Any untreated central nervous system (CNS) lesion. However, patients are eligible if: a) all known CNS lesions have been treated with radiotherapy or surgery and b) patient remained without evidence of CNS disease progression ≥ 4 weeks after treatment and c) patients must be off corticosteroid therapy for ≥ 2 weeks. * Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. * Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment. Note: Topical, inhaled, nasal and ophthalmic steroids are allowed. * Active, known or suspected autoimmune disease or a documented history of autoimmune disease Note: Patients with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted). * Allogenic bone marrow or solid organ transplant. * History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction. * Known history or current interstitial lung disease or non-infectious pneumonitis. * Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ. * Clinically significant infection, including known HIV or hepatitis C infection, or known hepatitis B surface antigen positivity. * Clinically significant ongoing infection. * Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 14 days or 5 half-lives before enrollment (whichever is longer) or is currently enrolled in the treatment stage of an investigational study. * A woman who is pregnant or breast-feeding, or a woman who is planning to become pregnant or a man who plans to father a child while enrolled in this study or within 150 days after the last dose of study agent. * Had hospitalization for infection or major surgery (eg, requiring general anesthesia) within 2 weeks before enrollment or have not fully recovered from surgery. Note: subjects with surgical procedures conducted under local anesthesia may participate. * History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following: * Recent myocardial infarction (within last 6 months) * Uncontrolled congestive heart failure * Unstable angina (within last 6 months) * Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular block (AV) block without a pacemaker)