A Study of Botensilimab in Participants With Metastatic Pancreatic Cancer

NCT05630183 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: C-800-22
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 36

Brief Summary

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.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Keywords

BOT; 1181; Immunotherapy; Pancreas; Gemcitabine; Nab-paclitaxel

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of Participants with Treatment-emergent Adverse Events

  First study dose through up 1 year

• Overall Survival

  Up to 2 years

• Complete Response

  Up to 2 years

• Progression-free Survival as Assessed by Investigator

  Up to 2 years

• Overall Response Rate

  Up to 2 years

Study Arms (3)

Part 1: Combination (Safety Lead-in Phase)

EXPERIMENTAL

Participants will receive botensilimab in combination with standard-of-care chemotherapy (nab-paclitaxel + gemcitabine).

Drug: Botensilimab; Drug: Gemcitabine; Drug: Nab-paclitaxel

Part 2: Combination

EXPERIMENTAL

Participants will receive botensilimab in combination standard-of-care chemotherapy (nab-paclitaxel + gemcitabine).

Drug: Botensilimab; Drug: Gemcitabine; Drug: Nab-paclitaxel

Part 2: Standard of Care

ACTIVE COMPARATOR

Participants will receive standard-of-care chemotherapy (nab-paclitaxel + gemcitabine).

Drug: Gemcitabine; Drug: Nab-paclitaxel

Interventions

Botensilimab DRUG

A fully human fragment crystallizable-enhanced monoclonal cytotoxic T lymphocyte antigen 4 antibody administered intravenously.

Also known as: AGEN1181

Part 1: Combination (Safety Lead-in Phase); Part 2: Combination

Gemcitabine DRUG

Standard-of-care chemotherapy administered intravenously.

Part 1: Combination (Safety Lead-in Phase); Part 2: Combination; Part 2: Standard of Care

Nab-paclitaxel DRUG

Standard-of-care chemotherapy administered intravenously.

Part 1: Combination (Safety Lead-in Phase); Part 2: Combination; Part 2: Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Agenus Inc.: lead

Study Sites (36)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology

Newport Beach, California, 92663, United States

Location

UCLA Health - Santa Monica Cancer Care

Santa Monica, California, 90404, United States

Location

Medical Oncology Hematology Consultants (MOHC) - Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States

Location

Florida Cancer Specialist South

Fort Myers, Florida, 33901, United States

Location

Cancer Care Centers of Brevard

Palm Bay, Florida, 32909, United States

Location

Florida Cancer Specialist North

St. Petersburg, Florida, 22705, United States

Location

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

Location

Maryland Oncology Hematology

Columbia, Maryland, 21044, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Rogel Cancer Center, University of Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Minnesota Oncology

Minneapolis, Minnesota, 55404, United States

Location

Nebraska Medicine-Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II*

Las Vegas, Nevada, 89144, United States

Location

John Theurer Cancer Center at Hackensack

Hackensack, New Jersey, 07601, United States

Location

Atlantic Health Systems, Morristown

Morristown, New Jersey, 07960, United States

Location

Overlook Medical Center

Summit, New Jersey, 07901, United States

Location

Weill Cornell Medicine-New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medicine Sandra and Edward Meyer Cancer Center

New York, New York, 10065, United States

Location

Icahn School of Medicine at Mount Sinai Tisch Cancer Institute

New York, New York, 10128, United States

Location

Oncology Hematology Care - Eastgate

Cincinnati, Ohio, 45245, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Cincinnati, Ohio, 45245, United States

Location

Lifespan

Providence, Rhode Island, 02903, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology

Carrollton, Texas, 75010, United States

Location

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75247, United States

Location

TxO - Denison Cancer Center

Denison, Texas, 75020, United States

Location

The Center for Cancer & Blood Disorders: Fort Worth

Fort Worth, Texas, 76104, United States

Location

Northeast Texas Cancer & Research Institute

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates - Brock Cancer Center

Norfolk, Virginia, 23502, United States

Location

Shenandoah Oncology

Winchester, Virginia, 22601, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

MeSH Terms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Medical Director

  Agenus Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2022
• First Posted: November 29, 2022
• Study Start: March 27, 2023
• Primary Completion: December 5, 2025
• Study Completion: December 5, 2025
• Last Updated: November 13, 2025

Record last verified: 2025-11

Locations

US (36)