A Study of Botensilimab in Participants With Metastatic Pancreatic Cancer

Open to people ages 18 years and up

• Histologically confirmed diagnosis of pancreatic ductal adenocarcinoma.
• Must have had disease progression on any version of FOLFIRINOX for metastatic disease.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Life expectancy of at least 3 months.
• Measurable disease on baseline imaging per RECIST 1.1 criteria.
• < Grade 2 pre-existing peripheral neuropathy per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0.
• Acceptable coagulation status as indicated by an international normalized ratio ≤ 1.5x institutional ULN, except participants on anticoagulation who can be included at the discretion of the investigator.
• Adequate organ function.
• Women of childbearing potential must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study drugs).
• Male participants with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study.

• Received more than one prior regimen (that is, FOLFIRINOX) for their metastatic disease.
• History of central nervous system metastasis.
• Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study drugs (that is, participants with a history of prior malignancy are eligible if treatment was completed at least 2 years prior to first dose of study drugs and the participant has no evidence of disease). Participants with history of prior early-stage basal/squamous cell skin cancer or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible.
• Uncontrolled intercurrent illness, including but not limited to clinically significant (that is, active) cardiovascular disease.
• Active, uncontrolled infections, requiring systemic intravenous anti-infective treatment within 2 weeks prior to first dose of study drugs.
• Major surgery within 4 weeks prior to signing of informed consent form (ICF).
• Prior treatment with an immune checkpoint inhibitor.
• Refractory ascites.
• Partial or complete bowel obstruction within the last 3 months prior to signing ICF, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction.
• Clinically significant gastrointestinal disorders.
• Treatment with one of the following classes of drugs within the delineated time window prior to first dose of study drugs:
  • Cytotoxic agent within 3 weeks.
  • Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or investigational drug, within 4 weeks, or 5 half-lives, whichever is shorter.
  • Small molecule/tyrosine kinase inhibitors within 14 days.
• Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to first dose of study drugs.
• SARS-CoV-2 vaccine < 7 days prior to first dose of study drugs.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Symptomatic interstitial lung disease (ILD), history of ILD or any lung disease which may interfere with detection and management of new immune-related pulmonary toxicity.
• History of allogeneic organ transplant.
• Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Participants with a condition requiring systemic treatment with either corticosteroids (> 10 milligrams [mg] daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days prior to first dose of study drugs. Inhaled or topical steroids, and adrenal replacement steroid doses (≤ 10 mg daily prednisone equivalent), are permitted in the absence of active autoimmune disease.
• Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years prior to first dose of study drugs (that is, with use of disease-modifying agents or immunosuppressive drugs).
• Pregnant or breastfeeding participants.
• Uncontrolled infection with human immunodeficiency virus.
• Known to be positive for hepatitis B (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection.
• Known active hepatitis C as determined by positive serology and confirmed by polymerase chain reaction.
• Dependence on total parenteral nutrition.
• Participants with concurrent diarrhea > grade 1 at time of randomization despite optimal treatment with standard of care pancreatic enzymes.
• Known active or latent tuberculosis (testing at screening not required).
• Any condition in the opinion of the principal investigator that might interfere with the participant's participation in the study or in the evaluation of the study results.
• Unwillingness or inability to comply with procedures required in this protocol.