A Study of Botensilimab in Participants With Metastatic Pancreatic Cancer

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Botensilimab; Drug: Gemcitabine; Drug: Nab-paclitaxel

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Newport Beach, California, United States, 92663
      • USC Norris Oncology
    • Santa Monica, California, United States, 90404
      • UCLA Health - Santa Monica Cancer Care
  • Delaware
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants (MOHC) - Helen F. Graham Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialist South
    • Palm Bay, Florida, United States, 32909
      • Cancer Care Centers of Brevard
    • St. Petersburg, Florida, United States, 22705
      • Florida Cancer Specialist North
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Illinois Cancer Specialists
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Rogel Cancer Center, University of Michigan Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medicine-Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II*
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health Systems, Morristown
    • Summit, New Jersey, United States, 07901
      • Overlook Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10021
      • Weill Cornell Medicine-New York Presbyterian Hospital
    • New York, New York, United States, 10065
      • Weill Cornell Medicine Sandra and Edward Meyer Cancer Center
    • New York, New York, United States, 10128
      • Icahn School of Medicine at Mount Sinai Tisch Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Oncology Hematology Care - Eastgate
    • Cincinnati, Ohio, United States, 45245
      • Sarah Cannon Research Institute at Tennessee Oncology
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute at Tennessee Oncology
  • Texas
    • Carrollton, Texas, United States, 75010
      • Texas Oncology
    • Dallas, Texas, United States, 75247
      • Baylor Charles A. Sammons Cancer Center
    • Denison, Texas, United States, 75020
      • TxO - Denison Cancer Center
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer & Blood Disorders: Fort Worth
    • Tyler, Texas, United States, 75702
      • Northeast Texas Cancer & Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Brock Cancer Center
    • Winchester, Virginia, United States, 22601
      • Shenandoah Oncology
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of pancreatic ductal adenocarcinoma. Note: fine needle aspirate/cytology of tumor in the presence of a pancreatic mass that confirms ductal adenocarcinoma is acceptable.
• Must have had disease progression on any version of FOLFIRINOX for metastatic disease (including onivyde + oxaliplatin + 5-fluorouracil [5-FU] + leucovorin [NALIRIFOX]). Clarification: Participant with initial diagnosis of locally advanced disease may be eligible if upon retrospective review of initial scans, previously unappreciated metastases are able to be identified; Investigator must provide documentation that participant had metastatic disease at the time the participant received FOLFIRINOX. Notes: Progression on a reduced or maintenance fluoropyrimidine based regimen in the metastatic setting is allowed (for example, leucovorin + 5-FU + oxaliplatin [FOLFOX], leucovorin + 5-FU + irinotecan [FOLFIRI], 5-FU, or capecitabine), provided the participant received at least 1 dose of all of the drugs in 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 Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). Because NCI CTCAE 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 general adverse 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 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. (Progression on a reduced or maintenance fluoropyrimidine-based regimen in the metastatic setting is allowed. [for example, FOLFOX, FOLFIRI, 5-FU, or capecitabine], provided the participant received at least 1 dose of all of the drugs in a FOLFIRINOX regimen.)
• History of central nervous system (CNS) metastasis or active CNS 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 of 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 or 5 half-lives (whichever is greater).
  • Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or investigational 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) infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to first dose of study drugs.
• Received a vaccine, including 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-mediated 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 the 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.
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival as Assessed by Investigator	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 investigator 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
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
Number of Participants with Treatment-emergent Adverse Events		First study dose through up 1 year
Complete Response	Complete response will be defined by RECIST 1.1 criteria and carbohydrate antigen 19-9 down to normal limits (from at least > 2 x upper limit of normal [ULN]). Cancer antigen 125 or carcinoembryonic antigen will be evaluated for non-expressors of carbohydrate antigen 19-9.	Up to 2 years
Progression-free Survival as Assessed by Investigator	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 investigator per RECIST 1.1, or death, whichever occurs first.	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 assessed by investigator 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 assessed by investigator 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 non-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 > 2 x ULN). Cancer antigen 125 or carcinoembryonic antigen will be evaluated for non-expressors of carbohydrate antigen 19-9.	Up to 2 years

Collaborators and Investigators

• Sponsor: Agenus Inc.
• Investigators: Study Director: Medical Director, Agenus Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2023
• Primary Completion (Estimated): December 5, 2025
• Study Completion (Estimated): December 5, 2025

Study Registration Dates

• First Submitted: November 18, 2022
• First Submitted That Met QC Criteria: November 18, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: November 12, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Gemcitabine; Immunotherapy; Pancreas; Nab-paclitaxel; BOT; 1181
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: C-800-22

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No