Clinical trial NCT05630183: A Study of Botensilimab in Participants With Metastatic Pancreatic Cancer
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
Keywords: BOT
1181
Immunotherapy
Pancreas
Gemcitabine
Nab-paclitaxel
Lead sponsor: Agenus Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-29
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival as Assessed by Independent Central Review Committee (IRC)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Number Of Participants With Treatment-emergent Adverse Events
timeFrame: First study dose through up 1 year
measure: Overall Survival
timeFrame: Up to 2 years
measure: Complete Response
timeFrame: Up to 2 years
measure: Progression-free Survival as Assessed by Investigators
timeFrame: Up to 2 years
measure: Overall Response Rate
timeFrame: Up to 2 years
measure: Duration Of Response
timeFrame: Up to 2 years
measure: Change From Baseline In Carbohydrate Antigen 19-9
timeFrame: Baseline, 2 years
measure: Rates Of Normalization Of Carbohydrate Antigen 19-9
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Newport Beach
country: United States
facility: USC Norris Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Health - Santa Monica Cancer Care
state: California
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants (MOHC) - Helen F. Graham Cancer Center
state: Delaware
city: Fort Myers
country: United States
facility: Florida Cancer Specialist South
state: Florida
city: Palm Bay
country: United States
facility: Cancer Care Centers of Brevard
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialist North
state: Florida
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Columbia
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Rogel Cancer Center, University of Michigan Medicine
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Medicine-Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Summerlin Medical Center II*
state: Nevada
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Health Systems, Morristown
state: New Jersey
city: Summit
country: United States
facility: Overlook Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine-New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine Sandra and Edward Meyer Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai Tisch Cancer Institute
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care - Eastgate
state: Ohio
city: Cincinnati
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Ohio
city: Providence
country: United States
facility: Lifespan
state: Rhode Island
city: Nashville
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Tennessee
city: Carrollton
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Baylor Charles A. Sammons Cancer Center
state: Texas
city: Denison
country: United States
facility: TxO - Denison Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: The Center for Cancer & Blood Disorders: Fort Worth
state: Texas
city: Tyler
country: United States
facility: Northeast Texas Cancer & Research Institute
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Brock Cancer Center
state: Virginia
city: Winchester
country: United States
facility: Shenandoah Oncology
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
affiliation: Agenus Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: