A Study of Botensilimab in Participants With Metastatic Pancreatic Cancer

Inclusion Criteria:

• Histologically confirmed diagnosis of pancreatic ductal adenocarcinoma. Note: fineneedle aspirate/cytology of tumor in the presence of a pancreatic mass that confirmsductal adenocarcinoma is acceptable.

• Must have had disease progression on any version of FOLFIRINOX for metastaticdisease (including onivyde + oxaliplatin + 5-fluorouracil [5-FU] + leucovorin [NALIRIFOX]). Clarification: Participant with initial diagnosis of locally advanceddisease may be eligible if upon retrospective review of initial scans, previouslyunappreciated metastases are able to be identified; Investigator must providedocumentation that participant had metastatic disease at the time the participantreceived FOLFIRINOX. Notes: Progression on a reduced or maintenance fluoropyrimidinebased regimen in the metastatic setting is allowed (for example, leucovorin + 5-FU +oxaliplatin [FOLFOX], leucovorin + 5-FU + irinotecan [FOLFIRI], 5-FU, orcapecitabine), provided the participant received at least 1 dose of all of the drugsin a FOLFIRINOX regimen.

• 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.

• A < Grade 2 pre-existing peripheral neuropathy per National Cancer Institute CommonTerminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). Because NCICTCAE v5.0 grading for peripheral neuropathy does not include guidance for "mild"neuropathy, these cases can be graded per the NCI CTCAE v5.0 grading for generaladverse events which includes "mild" under Grade 1.

• Acceptable coagulation status as indicated by an international normalized ratio ≤ 1.5 x institutional ULN, except participants on anticoagulation who can be includedat the discretion of the investigator.

• Adequate organ function.

• Women of childbearing potential must have a negative urine or serum pregnancy testat screening (within 72 hours of first dose of study drugs).

• Male participants with a female partner(s) of childbearing potential must agree touse highly effective contraceptive measures throughout the study.

Exclusion Criteria:

• Received more than one prior regimen (that is, FOLFIRINOX) for their metastaticdisease. (Progression on a reduced or maintenance fluoropyrimidine-based regimen inthe metastatic setting is allowed. [for example, FOLFOX, FOLFIRI, 5-FU, orcapecitabine], provided the participant received at least 1 dose of all of the drugsin a FOLFIRINOX regimen.)

• History of central nervous system (CNS) metastasis or active CNS metastasis.

• Concurrent malignancy (present during screening) requiring treatment or history ofprior malignancy active within 2 years prior to the first dose of study drugs (thatis, participants with a history of prior malignancy are eligible if treatment wascompleted at least 2 years prior to first dose of study drugs and the participanthas no evidence of disease). Participants with history of prior early-stagebasal/squamous cell skin cancer or noninvasive or in situ cancers who have undergonedefinitive treatment at any time are also eligible.

• Uncontrolled intercurrent illness, including but not limited to clinicallysignificant (that is, active) cardiovascular disease.

• Active, uncontrolled infections, requiring systemic intravenous anti-infectivetreatment 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 ofICF, signs/symptoms of bowel obstruction, or known radiologic evidence of impendingobstruction.

• Clinically significant gastrointestinal disorders.

• Treatment with one of the following classes of drugs within the delineated timewindow prior to first dose of study drugs:

• Cytotoxic agent within 3 weeks or 5 half-lives (whichever is greater).

• Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, orinvestigational drug, within 4 weeks, or 5 half-lives, whichever is shorter.

• Small molecule targeted therapies/tyrosine kinase inhibitors within 14 days or 5 half-lives (whichever is greater).

• Radiotherapy within 7 days.

• Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionwithin 10 days for mild or asymptomatic infections or 20 days for severe/criticalillness prior to first dose of study drugs.

• Received a vaccine, including SARS-CoV-2 vaccine, < 7 days prior to first dose ofstudy drugs.

• Known allergy or hypersensitivity to any of the study drugs or any of the study drugexcipients.

• Symptomatic interstitial lung disease (ILD), history of ILD, or any lung diseasewhich may interfere with detection and management of new immune-mediated pulmonarytoxicity.

• History of allogeneic organ transplant.

• Psychiatric or substance abuse disorders that would interfere with cooperation withthe requirements of the study.

• Participants with a condition requiring systemic treatment with eithercorticosteroids (> 10 milligrams [mg] daily prednisone equivalent) within 14 days oranother immunosuppressive medication within 30 days prior to the first dose of studydrugs. Inhaled or topical steroids, and adrenal replacement steroid doses (≤ 10 mgdaily prednisone equivalent), are permitted in the absence of active autoimmunedisease.

• Active autoimmune disease or history of autoimmune disease that required systemictreatment within 2 years prior to first dose of study drugs (that is, with use ofdisease-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 positivetest for HBV indicating acute or chronic infection.

• Known active hepatitis C as determined by positive serology and confirmed bypolymerase chain reaction.

• Dependence on total parenteral nutrition.

• Participants with concurrent diarrhea > grade 1 at time of randomization despiteoptimal treatment with standard of care pancreatic enzymes.

• Known active or latent tuberculosis.

• Any condition in the opinion of the principal investigator that might interfere withthe participant's participation in the study or in the evaluation of the studyresults.

• Unwillingness or inability to comply with procedures required in this protocol.