NC410 in Combination with Nivolumab and FOLFIRINOX Chemotherapy, with or without Ipilimumab, for the Treatment of Metastatic Pancreatic Cancer

Inclusion Criteria

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Metastatic histologically or cytologically confirmed pancreatic ductal adenocarcinoma. Subjects with islet cell neoplasms, adenosquamous and mixed histology will be excluded
• Have metastatic disease
• Patients must not have received prior systemic treatment for pancreatic cancer
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patient’s acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk as judged by the investigator
• Absolute neutrophil count ≥ 1,500/ mm^3
• Platelets ≥ 100,000/mm^3
• Hemoglobin ≥ 8 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x ULN
• Estimated glomerular filtration rate ≥ 30 mL/min/1.73m^2 (using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation or other equation per institutional guidelines, or based on 24-hour urine collection)
• 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]). Patients with a positive HCG due to tumor secretion may be permitted to enroll if lack of pregnancy can be documented (e.g. transvaginal ultrasound or serial HCG) and with approval by the principal investigator * A WOCBP must agree to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment
• A male participant must agree to use a contraception as detailed during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
• Participant understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form in accordance with regulatory and institutional guidelines. Consent must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report adverse event (AE), understand the drug dosing schedule and use of medications to control AE

Exclusion Criteria

• Subjects who have had prior chemotherapy for pancreatic cancer or prior chemotherapy within 5 years of enrollment for other cancer diagnoses
• Has received radiotherapy for pancreatic cancer
• Subjects who are receiving or have received any investigational agent or used an investigational device within 28 days prior to day 1 of treatment in this study
• Subject has undergone major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis or an aborted Whipple), within 28 days prior to day 1 of treatment in this study
• Is expected to require any other form of systemic or localized antineoplastic therapy while on study
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, or anti-Lag-3 antibodies
• Has received a live vaccine or live-attenuated vaccine within 28 days prior to the first dose of study drug. Administration of killed vaccine is allowed. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed
• Prior tissue or organ allograft regardless of need for immunosuppression, including corneal allograft. Exceptions can be approved by the principal investigator if loss of the graft is not a clinical concern. Patients with history of allogeneic bone marrow transplantation will be excluded
• Has uncontrolled acute or chronic medical illness
• Has history of central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has known additional malignancy that is progressing and requires active treatment * Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or other cancers that have undergone potentially curative therapy are not excluded
• Has active autoimmune disease. Subjects with Graves or Hashimoto’s disease, vitiligo, type I diabetes mellitus, psoriasis or other conditions not requiring systemic immunosuppressive treatment are permitted to enroll. Subjects requiring systemic treatment for autoimmune disease in the past must be approved by the principal investigator
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Requirement for daily supplemental oxygen
• Patients with a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
• Has a known history of human immunodeficiency virus (HIV). No HIV testing is required unless mandated by local health authority
• Has known active hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection. Patients who are hepatitis C antibody positive and viral load negative will be permitted to enroll. No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
• Subjects unable to undergo venipuncture and/or tolerate venous access
• Has known psychiatric or substance use disorder that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to study drug initiation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the case of a positive serum HCG test, a transvaginal ultrasound must be used to confirm lack of pregnancy