Immune-Based Therapies + Chemotherapy for Pancreatic Cancer

Overseen By Clinical Trials Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: HonorHealth Research Institute

Must not be taking: Warfarin, Digoxin

Disqualifiers: CNS metastasis, Active infections, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining new immune therapies with chemotherapy can enhance treatment responses in people with metastatic pancreatic cancer. The focus is on how two immune-based drugs, botensilimab (AGEN1181) and balstilimab (AGEN1884), work with standard chemotherapy and additional medications. Participants must have a confirmed diagnosis of metastatic pancreatic cancer and must not have received prior treatment for it. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive these new therapies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of botensilimab and balstilimab holds promise for treating various types of cancer. In previous studies, most patients tolerated these drugs well. Common side effects include tiredness and nausea, but these can be managed.

The chemotherapy drugs in this trial—nab-paclitaxel, gemcitabine, and cisplatin—have long been used in cancer treatment. They may cause side effects like low blood counts and hair loss, but doctors can manage these issues.

Chloroquine and celecoxib are also part of the treatment. Chloroquine, often used for malaria, can rarely cause vision changes. Celecoxib, a pain reliever, might cause stomach upset in some people.

Overall, while each drug has its own possible side effects, the combination has been studied, and safety information is available. Discuss any concerns with the research team before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine immune-based therapies with chemotherapy to tackle pancreatic cancer in a unique way. Unlike standard treatments such as FOLFIRINOX or gemcitabine with nab-paclitaxel, which primarily target cancer cells directly, this approach uses Balstilimab and Botensilimab to boost the body's immune response against the cancer. These drugs are immune checkpoint inhibitors that may help the immune system recognize and destroy cancer cells more effectively. By also incorporating chemotherapy and additional agents like chloroquine and celecoxib, this treatment aims to enhance the overall anti-cancer effect, potentially offering a new hope for improved outcomes in pancreatic cancer patients.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that the combination of two drugs, botensilimab and balstilimab, holds promise for treating various cancers, including pancreatic cancer. In other studies, this combination helped 42% of patients with a different advanced cancer live for at least two years, with an average survival time of about 21 months. These drugs enhance the body's immune system to better attack cancer cells. In this trial, participants will receive botensilimab and balstilimab alongside chemotherapy drugs such as nab-paclitaxel, gemcitabine, and cisplatin, as well as chloroquine and celecoxib. Although more research is needed specifically for pancreatic cancer, these early findings are encouraging. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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.

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)

You have a visible disease that can be measured using specific criteria.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Balstilimab
• Botensilimab
• Celecoxib
• Chloroquine Phosphate

Trial Overview 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.

How Is the Trial Designed?

Group I: Expansion Cohort-Botensilimab+balstilimab+nab-paclitaxel+gemcitabine+cisplatin+chloroquine+celecoxib Experimental Treatment 7 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 + celecoxib Experimental Treatment 7 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

Who Is Running the Clinical Trial?

HonorHealth Research Institute

Lead Sponsor

Trials

26

Recruited

940+

Translational Genomics Research Institute

Collaborator

Trials

36

Recruited

107,000+

University of Arizona

Collaborator

Trials

545

Recruited

161,000+

Agenus Inc.

Industry Sponsor

Trials

58

Recruited

4,900+

Published Research Related to This Trial

In a phase Ib trial involving 22 patients with metastatic pancreatic ductal adenocarcinoma, combinations of avelumab or talazoparib with binimetinib showed higher-than-expected rates of dose-limiting toxicity (DLT), particularly at the 45 mg dose, leading to dose adjustments.

Despite the safety concerns, the overall safety profiles of the combinations were consistent with those of the individual drugs, but no objective tumor responses were observed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab or talazoparib in combination with binimetinib in metastatic pancreatic ductal adenocarcinoma: dose-finding results from phase Ib of the JAVELIN PARP MEKi trial. Rodon Ahnert, J., Tan, DS., Garrido-Laguna, I., et al.[2023]

Hedgehog inhibition using IPI-926, when combined with gemcitabine, showed promising tolerance and potential effectiveness in treating pancreatic cancer, with further testing planned in a phase II trial.

The combination of gemcitabine with AZD7762 and the PI3K inhibitor BAY80-6946 both demonstrated acceptable safety profiles, indicating they may be viable options for future studies in pancreatic cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents for the treatment of pancreatic adenocarcinoma. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011. Cheng, H., Merika, E., Syrigos, KN., et al.[2011]

A study analyzing 2,364 cases of pancreatic adverse events (AEs) linked to immune checkpoint inhibitors (ICIs) found significant associations, particularly with ICI-associated pancreatitis and diabetes mellitus, indicating a notable risk for patients undergoing ICI treatment.

Combination therapy with ICIs showed a higher frequency of pancreatic AEs compared to monotherapy, suggesting that while the risk of these adverse events increases, the fatality rate remains lower, highlighting the importance of patient awareness regarding these potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic Adverse Events Associated With Immune Checkpoint Inhibitors: A Large-Scale Pharmacovigilance Analysis. Zhang, Y., Fang, Y., Wu, J., et al.[2022]

In a phase 3 study involving 800 patients with metastatic pancreatic cancer, ganitumab combined with gemcitabine did not improve overall survival (OS) compared to gemcitabine alone, with median OS of 7.2 months for placebo and similar results for both ganitumab doses (7.0 and 7.1 months).

The combination treatment showed manageable safety with no unexpected toxicities, but circulating biomarkers did not indicate any treatment effect on OS or progression-free survival (PFS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Fuchs, CS., Azevedo, S., Okusaka, T., et al.[2022]

In a systematic review of 59 randomized controlled trials involving 41,757 patients, immune checkpoint inhibitors (ICIs) were found to be associated with a 0.93% incidence of all-grade pancreatitis and higher rates of pancreatic enzyme elevations, indicating a notable risk of pancreatic adverse events (AEs) during treatment.

The study revealed that PD-1 inhibitors carry a greater risk of pancreatic AEs compared to PD-L1 inhibitors, and patients receiving dual ICI therapy face an even higher risk than those on single ICI therapy, highlighting the need for clinician awareness regarding these potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis. Zhao, Z., Zhang, W., Pang, L., et al.[2023]

The combination of ipilimumab and gemcitabine was found to be safe and tolerable for treating advanced pancreatic ductal adenocarcinoma (PDAC), with a maximum tolerated dose established at ipilimumab 3 mg/kg and gemcitabine 1,000 mg/m2.

Despite the safety of the regimen, the overall response rate was only 14%, indicating that adding ipilimumab does not significantly enhance the effectiveness compared to gemcitabine alone in advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study. Kamath, SD., Kalyan, A., Kircher, S., et al.[2022]

A study involving 448 patients with advanced cancers showed that immune checkpoint inhibitors, like anti-PD-1 and anti-CTLA4 therapies, are safe and well tolerated across different age groups, including those aged 75 and older.

Older patients (≥75 years) experienced fewer endocrine toxicities compared to younger patients, while they had a higher incidence of dermatological toxicities, indicating that age does not significantly increase the risk of severe adverse effects from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of age on the toxicity of immune checkpoint inhibition. Samani, A., Zhang, S., Spiers, L., et al.[2023]

The combination of cediranib and olaparib did not show clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who do not have a known BRCA mutation, as no objective responses were observed in the study of 19 patients.

Despite some patients experiencing stable disease for a median of 3.1 months, the overall survival was only 3.4 months, indicating limited efficacy of this treatment combination in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. Kim, JW., Cardin, DB., Vaishampayan, UN., et al.[2022]

In a study of 41 pancreas cancer patients treated with pembrolizumab, the median overall survival was 7.2 months, which is considered favorable compared to the benchmark of over 4 months.

Patients with specific genetic markers (dMMR, MSI-H, TMB-H, or Lynch syndrome) had a significantly lower risk of death, indicating that these biomarkers may help identify patients who could benefit more from pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. Storandt, MH., Tran, N., Martin, N., et al.[2023]

In a phase 1b clinical trial involving previously untreated patients with advanced pancreatic ductal adenocarcinoma (PDAC), ibrutinib monotherapy was found to enhance the immune response by increasing activated T cells and monocytes in the blood, indicating its potential to modulate the immune landscape.

However, when ibrutinib was combined with standard chemotherapy (gemcitabine and nab-paclitaxel), these beneficial immune changes were not observed, suggesting that the combination may limit the immunomodulatory effects of ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of myeloid and T cells in vivo by Bruton's tyrosine kinase inhibitor ibrutinib in patients with metastatic pancreatic ductal adenocarcinoma. Sinha, M., Betts, C., Zhang, L., et al.[2023]

In a study of 527 patients with advanced nonsmall cell lung cancer receiving PD-1 antibodies, age did not significantly affect the incidence of immune-related adverse events (irAEs) or overall survival, indicating that older patients may tolerate treatment similarly to younger ones.

However, patients aged 75 and older were more likely to have treatment interruptions due to irAEs, which correlated with lower overall survival, suggesting that while age does not affect the likelihood of irAEs, it may impact treatment continuity and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of age with differences in immune related adverse events and survival of patients with advanced nonsmall cell lung cancer receiving pembrolizumab or nivolumab. Ksienski, D., Wai, ES., Croteau, NS., et al.[2021]

In a phase II clinical trial involving 77 patients with advanced pancreatic cancer, the combination of the BTK inhibitor acalabrutinib and the anti-PD-1 antibody pembrolizumab was well tolerated but showed limited clinical activity, with an overall response rate of only 7.9%.

Despite the low efficacy, the treatment led to consistent reductions in myeloid-derived suppressor cells (MDSCs) in peripheral blood, suggesting a potential mechanism for improving immune response in pancreatic cancer that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of the Bruton tyrosine kinase inhibitor acalabrutinib, alone or with pembrolizumab in patients with advanced pancreatic cancer. Overman, M., Javle, M., Davis, RE., et al.[2023]

Citations

1. investor.agenusbio.com investor.agenusbio.com/news/news-details/2023/Agenus-Unveils-New-and-Updated-Botensilimab-Data-in-Colorectal-Pancreatic-Lung-Melanoma-and-Sarcoma/default.aspx

Agenus Unveils New and Updated Botensilimab Data in ... Agenus Unveils New and Updated Botensilimab Data in Colorectal, Pancreatic, Lung, Melanoma, and Sarcoma. October 22, 2023. Download ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609826/

Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is ... Botensilimab Effectively Treats Multiple Human Cancers. We have previously reported clinical results from an ongoing expanded phase I trial ( ...

3. onclive.com onclive.com/view/fc-enhanced-agents-may-expand-anti-ctla-4-approaches-in-gi-cancers

Fc-Enhanced Agents May Expand Anti–CTLA-4 ... - OncLive Botensilimab, combined with balstilimab, showed promising efficacy in HCC and CRC, with ongoing trials in pancreatic cancer. Vilastobart ...

4. cancernetwork.com cancernetwork.com/view/botensilimab-balstilimab-elicits-sustained-efficacy-in-mss-metastatic-crc

Botensilimab/Balstilimab Elicits Sustained Efficacy in MSS ... The combination attained a 42% 2-year survival rate as well as a median overall survival of 20.9 months among 123 patients with MSS metastatic ...

5. oncodaily.com oncodaily.com/oncolibrary/immune-oncology/battman-trial-bot-bal-q4

BOT/BAL Advancements, BATTMAN Trial, FDA Approval ... Clinical data have demonstrated strong efficacy in nine metastatic cancers, including colorectal, melanoma, and non-small cell lung cancer.

6. dana-farber.org dana-farber.org/clinical-trials/19-132

A Phase 1 Study of AGEN1181, an Fc-Engineered Anti- ... This study is an open-label, Phase 1, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) profiles

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06268015

NCT06268015 | Botensilimab and Balstilimab Optimization ... This is a single-arm, interventional, pilot clinical trial. Fifteen evaluable patients will have tumor-informed ctDNA testing at baseline and start ...

8. oncodaily.com oncodaily.com/oncolibrary/botensilimab-and-balstilimab-fda-jul25

Botensilimab and Balstilimab Achieves 21-Month Survival ... Botensilimab and balstilimab, an investigational immunotherapy combination from Agenus Inc. (Nasdaq: AGEN), delivered a median overall survival of 21 months.