A Study of Botensilimab in Participants With Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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The goal of this clinical trial is to test if the addition of botensilimab to standard chemotherapy improves the efficacy compared to just chemotherapy alone in participants with metastatic pancreatic cancer. One group of participants will only receive chemotherapy while a second group of participants will receive botensilimab and chemotherapy.

Detailed Description
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This will be a prospective, multicenter, clinical trial of botensilimab in combination with nab-paclitaxel + gemcitabine or nab-paclitaxel + gemcitabine alone. The trial will be conducted in 2 parts. Part 1 will be a safety lead-in to establish the safety and dose of botensilimab for Part 2. Part 2 will be a randomized, open-label assessment of botensilimab (at the dose level determined in Part 1).

Official Title
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A Randomized, Open-Label, Phase II Trial of Nab-paclitaxel + Gemcitabine With or Without Botensilimab (AGEN1181) in Patients With Metastatic Pancreatic Cancer Who Have Progressed on Prior 5FU + Leucovorin + Irinotecan + Oxaliplatin (FOLFIRINOX)

Conditions
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Metastatic Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: Botensilimab
* Drug: Gemcitabine
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Combination (Safety Lead-in Phase)<br>Participants will receive botensilimab in combination with standard-of-care chemotherapy (nab-paclitaxel + gemcitabine). | Drug: Botensilimab<br>* A fully human fragment crystallizable-enhanced monoclonal cytotoxic T lymphocyte antigen 4 antibody administered intravenously.<br>* Other names: AGEN1181;Drug: Gemcitabine<br>* Standard-of-care chemotherapy administered intravenously.<br>Drug: Nab-paclitaxel<br>* Standard-of-care chemotherapy administered intravenously.<br>|
| Experimental: Part 2: Combination<br>Participants will receive botensilimab in combination standard-of-care chemotherapy (nab-paclitaxel + gemcitabine). | Drug: Botensilimab<br>* A fully human fragment crystallizable-enhanced monoclonal cytotoxic T lymphocyte antigen 4 antibody administered intravenously.<br>* Other names: AGEN1181;Drug: Gemcitabine<br>* Standard-of-care chemotherapy administered intravenously.<br>Drug: Nab-paclitaxel<br>* Standard-of-care chemotherapy administered intravenously.<br>|
| Active Comparator: Part 2: Standard of Care<br>Participants will receive standard-of-care chemotherapy (nab-paclitaxel + gemcitabine). | Drug: Gemcitabine<br>* Standard-of-care chemotherapy administered intravenously.<br>Drug: Nab-paclitaxel<br>* Standard-of-care chemotherapy administered intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival will be defined as the time from the date of randomization to the date of the first objectively documented tumor progression, assessed by investigators per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), or death, whichever occurs first. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants With Treatment-emergent Adverse Events |  | First study dose through up 1 year | 
| Overall Survival | Overall survival will be defined as the time from the date of randomization to the date of death due to any cause. | Up to 2 years | 
| Complete Response | Complete response will be defined by RECIST 1.1 criteria and carbohydrate antigen 19-9 down to normal limits (from at least > 2x upper limit of normal [ULN]). Cancer antigen 125 or carcinoembryonic antigen will be evaluated for participants who are not expressors of carbohydrate antigen 19-9. | Up to 2 years | 
| Overall Response Rate | Overall response rate will be defined as the proportion of participants whose best overall response is complete response or partial response per RECIST v1.1. | Up to 2 years | 
| Duration Of Response | Duration of response will be defined as the time from the first determination of an objective response per RECIST v1.1, until the first documentation of progression or death, whichever occurs first. | Up to 2 years | 
| Change From Baseline In Carbohydrate Antigen 19-9 | Change in carbohydrate antigen 19-9 will be evaluated until progressive disease, death, date of last tumor assessment, or start of new anti-cancer therapy. Cancer antigen 125 or carcinoembryonic antigen will be evaluated for participants who are not expressors of carbohydrate antigen 19-9. | Baseline, 2 years | 
| Rates Of Normalization Of Carbohydrate Antigen 19-9 | Carbohydrate antigen 19-9 normalization will be defined as a value of carbohydrate antigen 19-9 down to normal limits (from at least > 2x ULN). Cancer antigen 125 or carcinoembryonic antigen will be evaluated for participants who are not expressors of carbohydrate antigen 19-9. | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BOT, 1181, Immunotherapy, Pancreas, Gemcitabine, Nab-paclitaxel