An Open-label, Phase I Trial With Expansion Cohort of Nab-Paclitaxel + Gemcitabine + Cisplatin + Botensilimab (AGEN1811) + Balsilimab (AGEN2034) + Chloroquine + Celecoxib in Patients With Previously Untreated Metastatic Pancreatic Cancer
The goal of this investigator initiated interventional study is to improve the response to the anticancer treatments (chemotherapy) in people who have previously untreated metastatic pancreas cancer. The main question it aims to answer is: • Do new types of immune-based therapies, called botensilimab, and balstilimab, when given in combination with chemotherapy consisting of nab-paclitaxel + gemcitabine + cisplatin, and oral medications of chloroquine and celecoxib help patients with previously untreated metastatic pancreatic cancer? Participants will be administered two immune-based therapies: * Botensilimab (also referred to as AGEN1811) * Balstilimab (also referred to as AGEN2034) Patients will be evaluated when given in combination with: * Triple chemotherapy (nab-paclitaxel + gemcitabine + cisplatin), plus two oral medications: * chloroquine * celecoxib
• Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
• ≥ 18 years of age.
• Histologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix A).
• Life expectancy of at least 3 months.
• Measurable disease on baseline imaging per RECIST 1.1 criteria.
• \< Grade 2 pre-existing peripheral neuropathy per NCI CTCAE, Version 5.0.
• Acceptable coagulation status as indicated by an international normalized ratio (INR)
‣ 1.5 times institutional upper limit of normal (ULN), except patients on anticoagulation who can be included at the discretion of the investigator.
• Adequate organ function defined as the following laboratory values within 7 days prior to first dose of study drugs, except where noted below:
∙ Neutrophils \> 1500/μL (stable off any growth factor within 4 weeks prior to first dose of study drugs).
‣ Platelets \> 100 × 103/μL (transfusion to achieve this level is not permitted within 2 weeks prior to first dose of study drugs).
‣ Hemoglobin \> 9.0 g/dL (transfusion to achieve this level is not permitted within 2 weeks prior to first dose of study drugs).
‣ Creatinine of \< 1.5mg/dL or Creatinine clearance ≥ 45 mL/min (measured or calculated per institutional standards).
‣ Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) \< 3.0 × ULN.
‣ Total bilirubin \< 1.25 × ULN (except patients with Gilbert syndrome who must have a total bilirubin level of \< 3.0 × ULN).
‣ Serum albumin ≥ 3.0 g/dL (must be confirmed within 3 days prior to first dose of study drugs).
⁃ Female patients of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study drugs).
⁃ WOCBP must agree to use highly effective contraceptive measures starting with the screening visit through 6 months after the last dose of study drug(s). Highly effective contraception is defined in Appendix B, Guidance on Contraception, or as stipulated in national or local guidelines. Non-childbearing potential is defined as:
∙ ≥ 50 years of age and has not had menses for greater than 1 year.
∙ Amenorrheic for ≥ 2 years without a hysterectomy and/or bilateral oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre- study (screening) evaluation.
∙ Status is post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation.
⁃ Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the screening visit through 6 months after the last dose of study drug(s) is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
⁃ Willing and able to comply with the requirements of the protocol.