AGEN1423 + Balstilimab With/Without Chemo for Pancreatic Cancer

Overseen By Bruno Bockorny, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bruno Bockorny

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Other pancreatic tumors, Active infection, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 2 years

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing new drugs AGEN1423 and Balstilimab, alone or with chemotherapy, for advanced pancreatic cancer patients who didn't respond to previous treatments. The treatment aims to boost the immune system to fight cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic steroid therapy or immunosuppressive therapy within 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination AGEN1423, Balstilimab, and chemotherapy for pancreatic cancer?

The combination of gemcitabine and albumin-bound paclitaxel (a form of chemotherapy) is a standard treatment for metastatic pancreatic cancer, showing a significant survival benefit compared to gemcitabine alone. This suggests that combining chemotherapy with other drugs like AGEN1423 and Balstilimab could potentially enhance treatment effectiveness. ^{1 2 3 4 5}

Is the combination of AGEN1423, Balstilimab, and chemotherapy safe for humans?

The safety of immune checkpoint inhibitors (like Balstilimab) has been studied, and they can cause immune-related side effects, including issues with the pancreas. Gemcitabine, a chemotherapy drug, has been used in various studies and is generally considered safe, but it can have side effects like any chemotherapy. There is no specific safety data available for AGEN1423 in the provided research. ^{4 6 7 8 9}

How is the drug AGEN1423 + Balstilimab with/without chemo unique for pancreatic cancer?

AGEN1423 + Balstilimab is unique because it combines immunotherapy agents, which aim to boost the body's immune response against cancer, with or without chemotherapy, offering a novel approach compared to traditional chemotherapy regimens like FOLFIRINOX or gemcitabine-based treatments that are typically used for pancreatic cancer. ^{3 5 10 11 12}

Research Team

Bruno Bockorny, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

This trial is for adults with advanced pancreatic ductal adenocarcinoma that's worsened after treatment. They must understand the study, sign consent, have good organ function, use contraception, and not be eligible for curative therapy. Exclusions include other active cancers or treatments, certain medical conditions like heart disease or lung issues, recent vaccines, pregnancy/breastfeeding intentions during the trial period.

Inclusion Criteria

My side effects from the last chemotherapy are mostly gone, except for hair loss and nerve issues.

You are expected to live for at least 3 more months.

Subjects must use effective contraception

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I have an immune system disorder or have taken steroids in the past week.

I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AGEN1423 plus Botensilimab for 4 cycles (8 weeks) followed by Botensilimab alone or with chemotherapy for up to 2 years

2 years

Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• AGEN1423
• Balstilimab
• Gemcitabine
• Nab-paclitaxel

Trial Overview The study tests AGEN1423 and Balstilimab combined with or without chemotherapy drugs gemcitabine and nab-paclitaxel in treating advanced pancreatic cancer. Participants will receive this treatment over two years and then be monitored for an additional year to assess safety and effectiveness.

Participant Groups

Group I: COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy Experimental Treatment 4 Interventions

Treatment is AGEN1423 plus Botensilimab in combination with gemcitabine and nab-paclitaxel for 2 cycles (8 weeks) followed by Botensilimab in combination with gemcitabine and nab-paclitaxel for up to 2 years. AGEN1423 will be administered in a total of 4 doses. Botensilimab will be administered once every 2 weeks.

Group II: COHORT 1: AGEN1423 Plus Botensilimab Experimental Treatment 2 Interventions

Treatment is AGEN1423 plus Botensilimab for 4 cycles (8 weeks) followed by Botensilimab alone for up to 2 years. AGEN1423 will be administered in a total of 4 doses. Botensilimab will be administered every 2 weeks.

Who Is Running the Clinical Trial?

Bruno Bockorny

Lead Sponsor

Trials

1

Recruited

20+

Bruno Bockorny, MD

Lead Sponsor

Trials

1

Recruited

20+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Agenus Inc.

Industry Sponsor

Trials

58

Recruited

4,900+

Findings from Research

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]

Despite extensive clinical trials over the past 20 years, gemcitabine has only slightly improved survival rates for pancreatic cancer patients, highlighting the need for more effective treatments.

Recent phase I trials presented at ASCO 2014 are exploring new drugs and combinations to address the challenges in treating locally advanced and metastatic pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trials in pancreatic cancer. Yu, E., Saif, MW., Huber, K.[2022]

FOLFIRINOX and gemcitabine plus albumin-bound paclitaxel are the leading chemotherapy regimens for metastatic pancreatic cancer, showing significant survival benefits over single-agent gemcitabine in phase III studies.

New treatments like nanoliposomal irinotecan plus infusional 5-fluorouracil are now approved for second-line therapy, allowing more patients to receive multiple lines of treatment, although the selection of therapies is still primarily based on clinical factors rather than molecular predictors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Management: Metastatic Disease. Ko, AH.[2018]

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 randomized phase II trial involving 106 patients with advanced pancreatic cancer, the combination of gemcitabine and S-1 significantly improved progression-free survival (PFS) to 5.4 months compared to 3.6 months with gemcitabine alone.

The combination therapy also showed a longer overall survival (OS) of 13.5 months versus 8.8 months for gemcitabine alone, although this difference was not statistically significant, indicating potential benefits without increased severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. Nakai, Y., Isayama, H., Sasaki, T., et al.[2022]

In a study of 137 patients with gemcitabine-refractory pancreatic cancer, the combination of irinotecan and S-1 (IRIS therapy) showed a median progression-free survival (PFS) of 3.5 months compared to 1.9 months for S-1 monotherapy, indicating a potential benefit in delaying disease progression.

The IRIS group also had a significantly higher response rate (18.3% vs 6.0%) compared to the S-1 monotherapy group, although it was associated with more frequent severe side effects like neutropenia and anorexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer. Ioka, T., Komatsu, Y., Mizuno, N., et al.[2022]

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 study of 72 patients with metastatic pancreatic cancer, the combination of lenalidomide and gemcitabine resulted in a 6-month overall survival rate of 37%, which does not show improvement over historical data for gemcitabine alone.

The treatment was associated with significant hematologic toxicities, including thrombocytopenia in 54% of patients and venous thromboembolic events in 28%, leading to dose modifications for many, suggesting that this combination may not be advisable for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with gemcitabine as first-line treatment for patients with metastatic carcinoma of the pancreas: a Sarah Cannon Research Institute phase II trial. Infante, JR., Arkenau, HT., Bendell, JC., et al.[2022]

The combination of galunisertib and durvalumab was found to be tolerable with no dose-limiting toxicities, and the recommended dose for further studies was established at 150 mg of galunisertib taken twice daily alongside durvalumab.

While the treatment showed a disease control rate of 25% among 32 patients, clinical activity was limited, suggesting that this combination may be more effective if used earlier in treatment or in patients selected based on specific biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer. Melisi, D., Oh, DY., Hollebecque, A., et al.[2021]

Most patients with pancreatic adenocarcinoma present with inoperable, metastatic disease, making systemic therapy the primary treatment option, with more therapeutic choices available than ever before.

Front-line treatments include FOLFIRINOX and gemcitabine plus nab-paclitaxel, while newer therapies like nanoliposomal irinotecan are approved for second-line treatment after progression on gemcitabine, highlighting the importance of personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Best practices for the treatment of metastatic pancreatic adenocarcinoma: the therapeutic landscape in 2017. Cinar, P., Ko, AH.[2018]

Four significant studies presented at the ASCO Annual Meeting explored new treatment combinations for pancreatic cancer, highlighting the need for improved therapeutic strategies due to the disease's poor prognosis.

The studies evaluated various combinations of existing drugs, such as gemcitabine with erlotinib and capecitabine, and assessed their efficacy and toxicity, indicating ongoing efforts to enhance treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First line treatment for metastatic pancreatic adenocarcinoma: looking for the step forward. Ramfidis, VS., Psyrri, A., Syrigos, KN., et al.[2022]

In a study of 41 patients with recurrent pancreatic cancer after gemcitabine treatment, those who experienced recurrence within 6 months had a lower overall survival rate (13.7 months) compared to those with recurrence after 6 months (19.8 months), indicating that timing of recurrence significantly impacts prognosis.

For patients with recurrence within 6 months, those treated with alternative chemotherapy regimens (fluoropyrimidine-containing) had better outcomes than those treated with gemcitabine, suggesting that alternative treatments may be more effective in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcome for systemic chemotherapy for recurrent pancreatic cancer after postoperative adjuvant chemotherapy. Taniyama, TK., Morizane, C., Nakachi, K., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Phase 1 trials in pancreatic cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical Management: Metastatic Disease. [2018]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Pancreatic Adverse Events Associated With Immune Checkpoint Inhibitors: A Large-Scale Pharmacovigilance Analysis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with gemcitabine as first-line treatment for patients with metastatic carcinoma of the pancreas: a Sarah Cannon Research Institute phase II trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer. [2021]

10. China pubmed.ncbi.nlm.nih.gov

Best practices for the treatment of metastatic pancreatic adenocarcinoma: the therapeutic landscape in 2017. [2018]

11. Italy pubmed.ncbi.nlm.nih.gov

First line treatment for metastatic pancreatic adenocarcinoma: looking for the step forward. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment outcome for systemic chemotherapy for recurrent pancreatic cancer after postoperative adjuvant chemotherapy. [2022]