A Study of Botensilimab in Participants With Metastatic Pancreatic Cancer

Metastatic Pancreatic Ductal Adenocarcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05630183
• Other study ID #: C-800-22
• Status: Recruiting
• Phase: Phase 2
• Start date: March 27, 2023
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Agenus Inc.
• Contact: Agenus, Inc. Clinical Trial Information
• Phone: 781-674-4265
• Email: clinicaltrialinfo[@]Agenusbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• Botensilimab
A fully human fragment crystallizable-enhanced monoclonal cytotoxic T lymphocyte antigen 4 antibody administered intravenously.
• Gemcitabine
Standard-of-care chemotherapy administered intravenously.
• Nab-paclitaxel
Standard-of-care chemotherapy administered intravenously.

Locations

Country	Name	City	State
United States	Rogel Cancer Center, University of Michigan Medicine	Ann Arbor	Michigan
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Texas Oncology	Carrollton	Texas
United States	Oncology Hematology Care - Eastgate	Cincinnati	Ohio
United States	Sarah Cannon Research Institute at Tennessee Oncology	Cincinnati	Ohio
United States	Maryland Oncology Hematology	Columbia	Maryland
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	TxO - Denison Cancer Center	Denison	Texas
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Florida Cancer Specialist South	Fort Myers	Florida
United States	The Center for Cancer & Blood Disorders: Fort Worth	Fort Worth	Texas
United States	John Theurer Cancer Center at Hackensack	Hackensack	New Jersey
United States	Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II*	Las Vegas	Nevada
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Minnesota Oncology	Minneapolis	Minnesota
United States	Atlantic Health Systems, Morristown	Morristown	New Jersey
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai Tisch Cancer Institute	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medicine Sandra and Edward Meyer Cancer Center	New York	New York
United States	Weill Cornell Medicine-New York Presbyterian Hospital	New York	New York
United States	Medical Oncology Hematology Consultants (MOHC) - Helen F. Graham Cancer Center	Newark	Delaware
United States	USC Norris Oncology	Newport Beach	California
United States	Virginia Oncology Associates - Brock Cancer Center	Norfolk	Virginia
United States	Nebraska Medicine-Nebraska Medical Center	Omaha	Nebraska
United States	Cancer Care Centers of Brevard	Palm Bay	Florida
United States	Lifespan	Providence	Rhode Island
United States	Florida Cancer Specialist North	Saint Petersburg	Florida
United States	UCLA Health - Santa Monica Cancer Care	Santa Monica	California
United States	HonorHealth	Scottsdale	Arizona
United States	Swedish Cancer Institute	Seattle	Washington
United States	Overlook Medical Center	Summit	New Jersey
United States	Northeast Texas Cancer & Research Institute	Tyler	Texas
United States	Shenandoah Oncology	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Agenus Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number Of Participants With Treatment-emergent Adverse Events		First study dose through up 1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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