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Pancreatic Cancer MetastaticPhase 1NCT06076837

The Seven Trial: Exploiting the Unfolded Protein Response

A Phase 1 study testing Botensilimab, Balstilimab and Chloroquine Phosphate in people with Pancreatic Cancer Metastatic and Pancreatic Adenocarcinoma Metastatic, run by HonorHealth Research Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Botensilimab, Balstilimab and Chloroquine Phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
9 Jan 2025to 22 Dec 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • < Grade 2 pre-existing peripheral neuropathy per NCI CTCAE, Version 5.0.
  • Acceptable coagulation status as indicated by an international normalized ratio (INR)
  • 1.5 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.
  • Total bilirubin < 1.25 × ULN (except patients with Gilbert syndrome who must have a total bilirubin level of < 3.0 × ULN).
  • Serum albumin ≥ 3.0 g/dL (must be confirmed within 3 days prior to first dose of study drugs).
  • Female patients of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study drugs).
  • WOCBP must agree to use highly effective contraceptive measures starting with the screening visit through 6 months after the last dose of study drug(s). Highly effective contraception is defined in Appendix B, Guidance on Contraception, or as stipulated in national or local guidelines. Non-childbearing potential is defined as:
  • ≥ 50 years of age and has not had menses for greater than 1 year.
  • Amenorrheic for ≥ 2 years without a hysterectomy and/or bilateral oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre- study (screening) evaluation.
  • Status is post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation.
  • Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the screening visit through 6 months after the last dose of study drug(s) is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
  • Willing and able to comply with the requirements of the protocol.

Who cannot join

  • 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.
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  • 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.
  • 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 t toxicity.
  • History of allogeneic organ transplant.
  • Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • Patients with a condition requiring systemic treatment with either corticosteroids (> 10 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 (i.e., with use of disease- modifying agents or immunosuppressive drugs).
  • Pregnant or breastfeeding patients.
  • Uncontrolled infection with HIV. Patients on stable highly active antiretroviral therapy ( (HAART) therapy with undetectable viral load and normal CD4 (Cluster of differentiation 4) counts for at least 6 months prior to signing ICF. Serological testing for HIV at screening is to be performed at the investigator's discretion based on individual patient's risk factors.
  • Known to be positive for hepatitis B (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Patients who are or have received anti-HBV therapy are eligible, permitting they have undetectable HBV DNA for at least 6 months prior to signing ICF. Serological testing for HBV at screening is to be performed at the investigator's discretion based on the individual patient's risk factors.
  • Known active hepatitis C (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or having received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to signing ICF. Serological testing for HCV at screening is to be performed at the investigator's discretion based on individual patient's risk factors.
  • Dependence on total parenteral nutrition.
  • Patients with concurrent diarrhea > grade 1 at time of enrollment 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 patient's participation in the study or in the evaluation of the study results.
  • Unwillingness or inability to comply with procedures required in this protocol.
  • History of coronary artery bypass graft.
  • Patients receiving warfarin or digoxin.
  • Presence of retinal or visual field changes of any etiology. Note: An ophthalmological examination to be performed within the 3 weeks of starting Chloroquine (C1/D1) to include: best corrected distance visual acuity (BCVA), an automated threshold visual field (VF) of the central 10 degrees (with retesting if an abnormality is noted), and spectral domain optical coherence tomography (SD-OCT). All of these parameters should be within normal parameters.
  • Known hypersensitivity to 4-aminoquinoline compounds (chloroquine, hydroxychloroquine, and amodiaquine).
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  • History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.
  • Patients who have demonstrated allergic-type reactions to sulfonamides.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Clinical Trials Nurse Navigator

    Scottsdale, Arizona, 85258

Other trials in United States

About this study

Official title: 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

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?
Read more

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
Read the detailed description

This Investigator Initiated Trial (IIT) is proposed based on our experience of obtaining high response rates with chemotherapy or chemotherapy + Programmed cell death protein 1 (PD1) checkpoint inhibitor in patients with previously untreated stage 4 pancreatic adenocarcinoma. However, investigators have hit a barrier as they have not been able to improve the complete response rate above 20% nor improve the 64% 2-year survival rate. For the most part ultimately, the patient's tumor progresses.

Pancreatic cancer relies upon unfolded protein response (UPR) to for survival. The endoplasmic reticulum has stress stressors with a variety of proteins that when activated during stress promote proteostasis and homeostasis which prevents apoptosis. While the UPR is able to achieve homeostasis, under prolonged and unresolved stress, the signaling pathway will lead to apoptosis. In pancreatic cancer, the UPR does play a role as it is upregulated to allow for greater survival. Prior cancer research has been focused on mitigating UPR in cancer through agents such as HSP90 inhibitors but this has not been successful. The hypothesis of this study is that by increasing ER stress and thus UPR that apoptosis occurs in pancreatic cancer by the use of these agents and improve the survival in individuals with advanced pancreatic cancer.

Visually it looks like this with three possibilities when tumor cells are under stress:

  1. They survive
  2. They go into dormancy
  3. They undergo apoptosis

Investigators seek to increase ER stress (UPR) to drive that system to apoptosis. To achieve the apoptosis, the investigators seek the maximum treatment approach with maximum chemo immunotherapy to stress the tumor cells (increase of ER stress /UPR) and use 2 agents to help block escape routes a) block autophagy via chloroquine and b) block microenvironment inflammation via celecoxib.

Being tested
Botensilimab, Balstilimab, Chloroquine Phosphate, Celecoxib, Nab paclitaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BotensilimabDrug

    Also called AGEN1811

    an Fc-engineered anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) monoclonal antibody

  • BalstilimabDrug

    Also called AGEN2034

    a human monoclonal immunoglobulin (Ig) G4 (IgG4) antibody, designed to block programmed cell death protein (PD-1) binding by PD-L1 and PD-L2

  • Chloroquine PhosphateDrug

    Also called Aralen

    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

  • CelecoxibDrug

    Also called Celebrex

    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)

  • Nab paclitaxelDrug

    microtubule inhibitor indicated for the treatment of Metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine

  • GemcitabineDrug

    a nucleoside metabolic inhibitor indicated as a single agent for the treatment of pancreatic cancer

  • CisplatinDrug

    platinum-based drug indicated for the treatment of advanced cancers

Study groups in NCT06076837
Study groupRoleWhat they receive
DoseEscalationBotensilimab+balstilimab+nab-paclitaxel+gemcitabine+cisplatin +chloroquine + celecoxibExperimentalBotensilimab 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
Receives: Drug: Botensilimab; Drug: Balstilimab; Drug: Chloroquine Phosphate; Drug: Celecoxib; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Cisplatin
Expansion Cohort-Botensilimab+balstilimab+nab-paclitaxel+gemcitabine+cisplatin+chloroquine+celecoxibExperimentalBotensilimab (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
Receives: Drug: Botensilimab; Drug: Balstilimab; Drug: Chloroquine Phosphate; Drug: Celecoxib; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 12 months

  2. 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).

    Measured: End of Study (up to 2 years)

Secondary outcomes (6)

  1. Complete Response (CR)

    To determine the preliminary efficacy of botensilimab at the MTD + balstilimab + triplet + chloroquine + celecoxib in patients with previously untreated metastatic pancreatic cancer. Complete Response (CR) rate as defined by CT scan using RECIST 1.1 criteria, the overall response rate (ORR), progression free survival (PFS) and overall survival (OS).

    Measured: End of Study (up to 2 years)

  2. Overall Response Rate (ORR)

    To determine the preliminary efficacy of botensilimab at the MTD + balstilimab + triplet + chloroquine + celecoxib in patients with previously untreated metastatic pancreatic cancer. Complete Response (CR) rate as defined by CT scan using RECIST 1.1 criteria, the overall response rate (ORR), progression free survival (PFS) and overall survival (OS).

    Measured: End of Study (up to 2 years)

  3. Progression free survival (PFS)

    To determine the preliminary efficacy of botensilimab at the MTD + balstilimab + triplet + chloroquine + celecoxib in patients with previously untreated metastatic pancreatic cancer. Complete Response (CR) rate as defined by CT scan using RECIST 1.1 criteria, the overall response rate (ORR), progression free survival (PFS) and overall survival (OS).

    Measured: End of Study (up to 2 years)

  4. Overall Survival (OS)

    To determine the preliminary efficacy of botensilimab at the MTD + balstilimab + triplet + chloroquine + celecoxib in patients with previously untreated metastatic pancreatic cancer. Complete Response (CR) rate as defined by CT scan using RECIST 1.1 criteria, the overall response rate (ORR), progression free survival (PFS) and overall survival (OS).

    Measured: End of Study (up to 2 years)

  5. Disease Control Rate (CR), Partial Response (PR), and Stable Disease (SD)

    To evaluate the disease control rate (CR, PR, and SD at 12 weeks) at the MTD of botensilimab + balstilimab + triplet + chloroquine + celecoxib in patients with previously untreated metastatic pancreatic cancer. Disease control rate (CR, PR, and SD at 12 weeks) using RECIST 1.1 criteria.

    Measured: 12 Weeks

  6. CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9)

    To evaluate the change in carbohydrate antigen 19-9 (CA 19-9) (or cancer antigen 125 [CA 125], or carcinoembryonic antigen [CEA] if not expressers of CA 19-9) in this patient population. Change from start of treatment CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9).

    Rates of normalization of CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9).

    Measured: End of Study (up to 2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Oct 2023
  2. Study start9 Jan 2025
  3. Primary completion22 Dec 2025
  4. Study completion22 Dec 2025

Why it stopped: The study was terminated early per the recommendation of the Data and Safety Monitoring Board (DSMB) after a planned interim analysis met pre-specified criteria for futility.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
(Part 1) Maximum Tolerated Dose (MTD) Safety Group; (Part 2) Expansion Cohort - Botensilimab MTD from Part 1
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06076837
Sponsor's protocol ID
HRI-2023 Magnificent 7
Status last verified
Jun 2026
First submitted
21 Sep 2023
Last updated
23 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 18023214

  • Botrus 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.

    PubMed 36614019

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Botensilimab, Balstilimab and Chloroquine Phosphate in people with Pancreatic Cancer Metastatic and Pancreatic Adenocarcinoma Metastatic, run by HonorHealth Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated early per the recommendation of the Data and Safety Monitoring Board (DSMB) after a planned interim analysis met pre-specified criteria for futility.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06076837, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.

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