Immune-Based Therapies + Chemotherapy for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: HonorHealth Research Institute
Must not be taking: Warfarin, Digoxin
Disqualifiers: CNS metastasis, Active infections, Autoimmune disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, patients receiving warfarin or digoxin are excluded, and those on certain immunosuppressive medications or corticosteroids may need to adjust their treatment. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination including Balstilimab, AGEN1884, Botensilimab, AGEN1181, Celecoxib, Celebrex, and Chloroquine Phosphate for pancreatic cancer?
Research suggests that combining immune-based therapies with chemotherapy, like the combination of ipilimumab and gemcitabine, may help overcome the resistance of pancreatic cancer to treatment by targeting the tumor's protective environment.
12345What safety data exists for immune-based therapies like Balstilimab and Botensilimab in humans?
Immune checkpoint inhibitors, which include drugs like Balstilimab and Botensilimab, have been linked to pancreatic side effects, although the specific details of these effects are not fully understood. Older adults may experience different side effects from these treatments, but they are often not well-represented in clinical trials, making it hard to assess safety for this group.
16789What makes the drug Balstilimab and Botensilimab unique for pancreatic cancer?
Balstilimab and Botensilimab are unique because they combine immune-based therapies with chemotherapy, potentially overcoming the resistance seen in pancreatic cancer due to its protective tumor environment. This approach aims to enhance the body's immune response against the cancer, which is different from traditional treatments that often rely solely on chemotherapy.
14101112Eligibility Criteria
This trial is for adults with untreated metastatic pancreatic cancer who have a life expectancy of at least 3 months, can perform daily activities (ECOG status 0 or 1), and agree to use effective contraception. They must not have had previous cancer treatments or certain health conditions like severe allergies, recent surgeries, active infections, or other cancers within the last two years.Inclusion Criteria
You are expected to live for at least 3 more months.
You have a visible disease that can be measured using specific criteria.
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)
+10 more
Exclusion Criteria
You have had allergic reactions to sulfonamide medications.
I have had cancer spread to my brain or spinal cord.
Your heart's electrical activity, measured by ECG, shows a QTcf longer than 450 milliseconds.
+31 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a combination of botensilimab, balstilimab, nab-paclitaxel, gemcitabine, cisplatin, chloroquine, and celecoxib to increase ER stress and drive apoptosis in tumor cells.
12 months
Follow-up
Participants are monitored for safety, tolerability, and effectiveness of the treatment, including progression-free survival and overall survival.
up to 2 years
Quality of Life Assessment
Participants' self-reported quality of life and pain levels are evaluated using the MD Anderson Symptom Inventory and Brief Pain Inventory.
up to 3 years
Participant Groups
The study tests if combining new immune therapies botensilimab and balstilimab with chemotherapy (nab-paclitaxel + gemcitabine + cisplatin) and oral drugs chloroquine and celecoxib improves treatment outcomes in metastatic pancreatic cancer patients.
2Treatment groups
Experimental Treatment
Group I: Expansion Cohort-Botensilimab+balstilimab+nab-paclitaxel+gemcitabine+cisplatin+chloroquine+celecoxibExperimental Treatment7 Interventions
Botensilimab (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
Group II: DoseEscalationBotensilimab+balstilimab+nab-paclitaxel+gemcitabine+cisplatin +chloroquine + celecoxibExperimental Treatment7 Interventions
Botensilimab 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Clinical Trials Nurse NavigatorScottsdale, AZ
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Who Is Running the Clinical Trial?
HonorHealth Research InstituteLead Sponsor
Translational Genomics Research InstituteCollaborator
University of ArizonaCollaborator
Agenus Inc.Industry Sponsor
References
A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. [2022]This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer.
Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. [2022]Cediranib and olaparib combination did not result in clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma without known BRCA mutation.
Randomized phase II study of the Bruton tyrosine kinase inhibitor acalabrutinib, alone or with pembrolizumab in patients with advanced pancreatic cancer. [2023]The immunosuppressive desmoplastic stroma of pancreatic cancer represents a major hurdle to developing an effective immune response. Preclinical studies in pancreatic cancer have demonstrated promising anti-tumor activity with Bruton tyrosine kinase (BTK) inhibition combined with programmed cell death receptor-1 (PD-1) blockade.
Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study. [2022]Pancreatic ductal adenocarcinoma (PDAC) remains resistant to chemotherapy and immunotherapy individually because of its desmoplastic stroma and immunosuppressive tumor microenvironment. Synergizing cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint blockade with chemotherapy could overcome these barriers. Here we present results of a phase Ib trial combining ipilimumab and gemcitabine in advanced PDAC.
Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. [2023]Pembrolizumab confers minimal benefit to most patients with pancreas cancer. We explored survival and patient treatment burden (for example, death within 14 days of therapy) in a subgroup who had early access to pembrolizumab .
Pancreatic Adverse Events Associated With Immune Checkpoint Inhibitors: A Large-Scale Pharmacovigilance Analysis. [2022]Backgrounds: Immune checkpoint inhibitors (ICIs) are considered cornerstones of oncology treatment with durable anti-tumor efficacy, but the increasing use of ICIs is associated with the risk of developing immune-related adverse events (irAEs). Although ICI-associated pancreatic adverse events (AEs) have been reported in patients treated with ICIs, the clinical features and spectrum of pancreatic AEs are still not well-defined. Therefore, this study aimed to identify the association between pancreatic AEs and ICIs treatments and to characterize the main features of ICI-related pancreatic injury (ICIPI) based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.
Impact of age on the toxicity of immune checkpoint inhibition. [2023]Indications for immune checkpoint inhibitor therapy are increasing. As the population ages, many patients receiving such drugs will be older adults. Such patients are under-represented in clinical trials, and therefore the safety of immune checkpoint inhibitors in this population has not been adequately assessed. A retrospective multicenter analysis of toxicities was performed in patients with advanced or metastatic solid cancers receiving anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies across three age cohorts (
Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis. [2023]This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.
Association of age with differences in immune related adverse events and survival of patients with advanced nonsmall cell lung cancer receiving pembrolizumab or nivolumab. [2021]To explore the association of age with development of immune related adverse events (irAE) and survival in patients with advanced nonsmall cell lung cancer (aNSCLC) receiving programmed cell death 1 antibodies (PD-1 Ab) outside of clinical trials.
Avelumab or talazoparib in combination with binimetinib in metastatic pancreatic ductal adenocarcinoma: dose-finding results from phase Ib of the JAVELIN PARP MEKi trial. [2023]Combinations of avelumab [anti-programmed death-ligand 1 (anti-PD-L1)] or talazoparib [poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor] with binimetinib (MEK inhibitor) were expected to result in additive or synergistic antitumor activity relative to each drug administered alone. Here, we report phase Ib results from JAVELIN PARP MEKi, which investigated avelumab or talazoparib combined with binimetinib in metastatic pancreatic ductal adenocarcinoma (mPDAC).
Novel agents for the treatment of pancreatic adenocarcinoma. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011. [2011]There are urgent needs to develop novel and more effective regimens to improve outcomes of pancreatic cancer given its dismal prognosis and limited treatment options. Several phase I clinical trials involving novel agents were recently presented at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting. It appears that hedgehog inhibition with IPI-926 was well-tolerated and might be effective in treating pancreatic cancer when combined with gemcitabine. The survival benefits will be tested in the following randomized phase II trial. The new combination of gemcitabine and blockade of checkpoint kinases with AZD7762 showed an acceptable safety profile. Furthermore, inhibition of PI3K by BAY80-6946 was well tolerated with PET-CT suggesting reduction in FDG uptake in some pancreatic cancer. The benefits of above novel agents/regimens need to be further tested in phase II trials.
Modulation of myeloid and T cells in vivo by Bruton's tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma. [2023]In preclinical studies of pancreatic ductal adenocarcinoma (PDAC), ibrutinib improved the antitumor efficacy of the standard of care chemotherapy. This led to a phase 1b clinical trial to determine the safety, tolerability, and immunologic effects of ibrutinib treatment in patients with advanced PDAC.