The Seven Trial: Exploiting the Unfolded Protein Response
An Open-label, Phase I Trial With Expansion Cohort of Nab-Paclitaxel + Gemcitabine + Cisplatin + Botensilimab (AGEN1811) + Balsilimab (AGEN2034) + Chloroquine + Celecoxib in Patients With Previously Untreated Metastatic Pancreatic Cancer
1 other identifier
interventional
6
1 country
1
Brief Summary
The goal of this investigator initiated interventional study is to improve the response to the anticancer treatments (chemotherapy) in people who have previously untreated metastatic pancreas cancer. The main question it aims to answer is:
- Do new types of immune-based therapies, called botensilimab, and balstilimab, when given in combination with chemotherapy consisting of nab-paclitaxel + gemcitabine + cisplatin, and oral medications of chloroquine and celecoxib help patients with previously untreated metastatic pancreatic cancer? Participants will be administered two immune-based therapies:
- Botensilimab (also referred to as AGEN1811)
- Balstilimab (also referred to as AGEN2034) Patients will be evaluated when given in combination with:
- Triple chemotherapy (nab-paclitaxel + gemcitabine + cisplatin), plus two oral medications:
- chloroquine
- celecoxib
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jan 2025
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 21, 2023
CompletedFirst Posted
Study publicly available on registry
October 11, 2023
CompletedStudy Start
First participant enrolled
January 9, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
January 12, 2026
January 1, 2026
1.4 years
September 21, 2023
January 8, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD)
To determine the maximum tolerated dose (MTD) of botensilimab when given in combination with balstilimab + triplet chemotherapy regimen (consisting of nab-paclitaxel + gemcitabine + cisplatin) + chloroquine + celecoxib to be used in Part 2-Dose Expansion. MTD will be defined at the dose of botensilimab at which no more than 1 of 6 evaluable patients experiences a dose-limiting toxicity (DLT).
12 months
Safety and Tolerability of botensilimab in combination with balstilimab + triplet + chloroquine + celecoxib. Treatment-related toxicities as per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTC AE V5.0).
To evaluate the safety and tolerability of botensilimab in combination with balstilimab + triplet + chloroquine + celecoxib. Treatment-related toxicities as per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTC AE V5.0).
End of Study (up to 2 years)
Secondary Outcomes (6)
Complete Response (CR)
End of Study (up to 2 years)
Overall Response Rate (ORR)
End of Study (up to 2 years)
Progression free survival (PFS)
End of Study (up to 2 years)
Overall Survival (OS)
End of Study (up to 2 years)
Disease Control Rate (CR), Partial Response (PR), and Stable Disease (SD)
12 Weeks
- +1 more secondary outcomes
Other Outcomes (5)
Quality of Life: MD Anderson Symptom Inventory (MDASI-GI)
through study completion (up to 3 years)
Pain Levels: Brief Pain Inventory (BPI)
through study completion (up to 3 years)
Determination of the Effects of the regimen - ER stress (unfolded protein response) level assessment
through study completion (up to 3 years)
- +2 more other outcomes
Study Arms (2)
DoseEscalationBotensilimab+balstilimab+nab-paclitaxel+gemcitabine+cisplatin +chloroquine + celecoxib
EXPERIMENTALBotensilimab 50 mg IV, Balstilimab 240 mg, nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 +cisplatin 25 mg/m2; Chloroquine phosphate 500 mg po (300 mg equivalent chloroquine base); Celecoxib 200 mg po twice daily (BID) on Famotidine 20 mg po BID Aspirin 81 mg
Expansion Cohort-Botensilimab+balstilimab+nab-paclitaxel+gemcitabine+cisplatin+chloroquine+celecoxib
EXPERIMENTALBotensilimab (MTD TBD), Balstilimab 240 mg IV, nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 +cisplatin 25 mg/m2 IV infusion ; Chloroquine phosphate 500 mg po (300 mg equivalent chloroquine base),Celecoxib 200 mg po twice daily (BID); Famotidine 20 mg po BID Aspirin 81 mg
Interventions
microtubule inhibitor indicated for the treatment of Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine
a nucleoside metabolic inhibitor indicated as a single agent for the treatment of pancreatic cancer
an Fc-engineered anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) monoclonal antibody
a human monoclonal immunoglobulin (Ig) G4 (IgG4) antibody, designed to block programmed cell death protein (PD-1) binding by PD-L1 and PD-L2
an antimalarial agent, that is being used in this patient population to sensitize cancer cells to chemotherapy and leads to anticancer effects through inhibiting autophagy
a second-generation selective Cyclooxygenase 2 (COX-2) inhibitor, is being used in this patient population to enhance the therapeutic effect of cisplatin by inhibiting the expression of COX-2 as well as inhibit anti-apoptotic gene BCL-2 (B-cell lymphoma 2)
platinum-based drug indicated for the treatment of advanced cancers
Eligibility Criteria
You may qualify if:
- Voluntarily agree to participate by giving signed, dated, and written informed consent prior to any study-specific procedures.
- ≥ 18 years of age.
- Histologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix A).
- Life expectancy of at least 3 months.
- Measurable disease on baseline imaging per RECIST 1.1 criteria.
- \< Grade 2 pre-existing peripheral neuropathy per NCI CTCAE, Version 5.0.
- Acceptable coagulation status as indicated by an international normalized ratio (INR)
- times institutional upper limit of normal (ULN), except patients on anticoagulation who can be included at the discretion of the investigator.
- Adequate organ function defined as the following laboratory values within 7 days prior to first dose of study drugs, except where noted below:
- Neutrophils \> 1500/μL (stable off any growth factor within 4 weeks prior to first dose of study drugs).
- Platelets \> 100 × 103/μL (transfusion to achieve this level is not permitted within 2 weeks prior to first dose of study drugs).
- Hemoglobin \> 9.0 g/dL (transfusion to achieve this level is not permitted within 2 weeks prior to first dose of study drugs).
- Creatinine of \< 1.5mg/dL or Creatinine clearance ≥ 45 mL/min (measured or calculated per institutional standards).
- Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) \< 3.0 × ULN.
- +9 more criteria
You may not qualify if:
- Patients must have received no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-Fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and development of metastatic disease and no lingering toxicities are present.
- History of central nervous system (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 (i.e., patients 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 patient has no evidence of disease). Patients 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.
- QTc Derived From Fridericia's Formula (QTcf) \> 450 ms on electrocardiogram (ECG)
- Uncontrolled intercurrent illness, including but not limited to clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥ III), or serious uncontrolled cardiac arrhythmia requiring medication. Patients with history of coronary bypass procedure are ineligible.
- 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 defined as requiring 2 or more therapeutic paracenteses within the last 4 weeks or ≥ 4 within the last 90 days or ≥ 1 time within the last 2 weeks prior to signing of ICF or requiring diuretics intended to treat ascites within 2 weeks of signing of ICF.
- 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 (GI) disorders including:
- GI perforation or unhealed ulcerations \< 6 months prior to signing of ICF. Patients must have documented evidence (e.g., upper endoscopy, colonoscopy) of completely healed area of prior perforation or ulceration.
- Clinically significant GI bleeding \< 3 months prior to signing of informed consent.
- History of active Crohn's disease or ulcerative colitis.
- 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.
- +23 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- HonorHealth Research Institutelead
- University of Arizonacollaborator
- Agenus Inc.collaborator
Study Sites (1)
Clinical Trials Nurse Navigator
Scottsdale, Arizona, 85258, United States
Related Publications (2)
Malhotra JD, Kaufman RJ. The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol. 2007 Dec;18(6):716-31. doi: 10.1016/j.semcdb.2007.09.003. Epub 2007 Sep 8.
PMID: 18023214BACKGROUNDBotrus G, Miller RM, Uson Junior PLS, Kannan G, Han H, Von Hoff DD. Increasing Stress to Induce Apoptosis in Pancreatic Cancer via the Unfolded Protein Response (UPR). Int J Mol Sci. 2022 Dec 29;24(1):577. doi: 10.3390/ijms24010577.
PMID: 36614019BACKGROUND
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 21, 2023
First Posted
October 11, 2023
Study Start
January 9, 2025
Primary Completion (Estimated)
June 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
January 12, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share