Immunotherapy for Pancreatic Cancer

Overseen By Joann Santmyer, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Steroids

Disqualifiers: Autoimmune disease, Active infection, Cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores different immunotherapy combinations to treat surgically removable pancreatic cancer. It aims to evaluate the effectiveness of these treatments in boosting the body's immune system to fight cancer before and after surgery. Participants will receive various therapies, including vaccines and medications like nivolumab, an immunotherapy drug designed to enhance the immune response. Suitable candidates have newly diagnosed or suspected pancreatic cancer that can be surgically removed and have not received prior cancer treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 have received any anti-cancer treatment or immunotherapy for pancreatic cancer, and you must not be using systemic steroids within 14 days before the trial.

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

A previous study demonstrated the safety of the GVAX pancreatic cancer vaccine for patients, with no major safety concerns and good tolerance among recipients. Research shows that nivolumab, another treatment in the trial, can cause some immune-related side effects, such as inflammation of the pancreas or colon, but these are generally manageable. Studies have examined the safety of urelumab, also part of the trial, and found it can be safe at lower doses. Lastly, BMS-986253 has been studied and found to be safe overall, though data specific to pancreatic cancer remains limited.

Overall, these treatments have undergone prior study and are considered safe for use in trials. However, like any treatment, side effects can occur. Participants are closely monitored in trials to manage any issues that might arise. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pancreatic cancer, which often involve surgery, chemotherapy, and radiation, the investigational treatments in this trial focus on harnessing the immune system to fight the cancer. Researchers are excited about these treatments because they include innovative components like the GVAX pancreatic cancer vaccine and the use of drugs like nivolumab and urelumab, which are designed to boost the body's natural defenses. Additionally, the inclusion of BMS-986253 in one of the treatment arms adds another layer of immune modulation. This approach has the potential to offer a more targeted attack on cancer cells, potentially resulting in better outcomes and fewer side effects compared to traditional therapies.

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

Research has shown that the GVAX pancreatic cancer vaccine, which participants in this trial may receive, can help the immune system fight cancer cells. In some studies, patients lived longer. Nivolumab, another treatment option in this trial, has shown promise when combined with chemotherapy, helping some patients survive longer, especially if the cancer has certain markers. Urelumab, used in one of the trial arms with GVAX and nivolumab, is a newer treatment that aims to boost the immune response but has not been very successful on its own. BMS-986253, an anti-IL-8 antibody, is being tested in this trial to assess its effectiveness with other treatments, though it has not shown strong results by itself yet. Overall, these treatments in the various trial arms aim to strengthen the body's natural defenses against pancreatic cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Ana De Jesus-Acosta, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for people with a type of pancreatic cancer that can be surgically removed. Participants should be in good physical condition (ECOG 0-1), have proper organ function, and not have had any prior cancer treatments or immunotherapies for their pancreatic cancer. They must also agree to use birth control.

Inclusion Criteria

My tumor can be removed with surgery.

My organ functions are within normal ranges according to specific tests.

Must agree to use acceptable form of birth control

Exclusion Criteria

Pregnant or lactating

History of severe hypersensitivity reaction to any monoclonal antibody or known component of the study drugs

Oxygen saturation of <92% on room air by pulse oximetry

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive immunotherapy combinations including cyclophosphamide, nivolumab, urelumab, and GVAX vaccine prior to surgery

2 weeks

2 visits (in-person)

Surgery

Participants undergo pancreaticoduodenectomy

1 day

1 visit (in-person)

Adjuvant Treatment

Participants receive post-surgery immunotherapy and chemoradiotherapy

6-10 weeks

Multiple visits (in-person)

Extended Treatment

Participants receive extended immunotherapy with nivolumab and urelumab, and GVAX vaccine

6 months

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986253
• Cyclophosphamide
• GVAX pancreatic cancer
• Nivolumab
• Urelumab

Trial Overview The study tests different combinations of immunotherapy drugs before and after surgery in patients with resectable pancreatic ductal adenocarcinoma. Drugs tested include Cyclophosphamide, GVAX, Urelumab, BMS-986253, and Nivolumab.

How Is the Trial Designed?

Group I: Arm D: BMS-986253 and Nivolumab Experimental Treatment 2 Interventions

Patients receive BMS-986253 and nivolumab on day 0 (Cycle 1), 15 days prior to surgery. 6-10 weeks after surgery, patients receive Cycle 2, with nivolumab on day 0 and BMS-986253 on days 0 and 14. Patients then receive standard adjuvant chemoradiotherapy. Approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive 4 additional 28-day cycles of immunotherapy, with Nivolumab on Day 0 and BMS-986253 on Days 0 and 14. Patients will then enter the extended treatment phase where they will receive nivolumab alone every 4 weeks for another 6 treatments.

Group II: Arm C: CY/GVAX with nivolumab and urelumab Experimental Treatment 4 Interventions

Patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and GVAX pancreatic cancer vaccine on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and the vaccine on day 1. Beginning approximately 28 days after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide, nivolumab, and urelumab on day 0 and GVAX on day 1. Treatment with cyclophosphamide, nivolumab, urelumab, and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive nivolumab and urelumab every 4 weeks for another 6 treatments as well as cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.

Group III: Arm B: CY/GVAX with nivolumab Experimental Treatment 3 Interventions

Patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and the vaccine on day 1. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide and nivolumab IV on day 0 and the vaccine on day 1. Treatment with cyclophosphamide, nivolumab, and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive nivolumab every 4 weeks for another 6 treatments as well as cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.

Group IV: Arm A: CY/GVAX alone Experimental Treatment 2 Interventions

Patients receive low-dose cyclophosphamide IV on day 0 and GVAX pancreatic cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Beginning approximately 1 month after vaccination, patients receive standard adjuvant chemoradiotherapy. Beginning approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Treatment with cyclophosphamide and the vaccine repeats every 28 days for 4 courses. Patients will then enter the extended treatment phase where they will receive cyclophosphamide on day 0, and GVAX on day 1 every 12 weeks for another 2 treatments.

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

The combination of GVAX and CRS-207 significantly improved overall survival in patients with metastatic pancreatic adenocarcinoma, with a median survival of 6.1 months compared to 3.9 months for those receiving only GVAX.

This treatment approach showed minimal toxicity, with the most common side effects being transient fevers and fatigue, indicating a favorable safety profile while enhancing immune responses against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. Le, DT., Wang-Gillam, A., Picozzi, V., et al.[2021]

In a study of 30 patients with advanced pancreatic ductal adenocarcinoma, combining ipilimumab (10 mg/kg) with the GVAX vaccine led to prolonged disease stabilization in 3 patients and a decline in CA19-9 levels, indicating a potential therapeutic benefit.

The combination treatment also showed a trend towards improved overall survival (5.7 months) compared to ipilimumab alone (3.6 months), suggesting that this approach may enhance the effectiveness of cancer immunotherapy, although further studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. Le, DT., Lutz, E., Uram, JN., et al.[2022]

The neoadjuvant treatment with the GVAX vaccine, either alone or with low-dose cyclophosphamide, is safe and does not increase surgical complications in patients with resectable pancreatic ductal adenocarcinoma (PDAC).

Patients receiving GVAX alone showed a trend toward longer overall survival (35.0 months) compared to historical controls, suggesting potential benefits of this immunotherapy, while the addition of cyclophosphamide was associated with shorter disease-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma. Zheng, L., Ding, D., Edil, BH., et al.[2022]

In a study involving 93 patients with metastatic pancreatic cancer, combining GVAX vaccine and cyclophosphamide with nivolumab (Arm A) did not significantly improve overall survival compared to the same treatment without nivolumab (Arm B), with median survival times of 5.9 and 6.1 months, respectively.

Despite not meeting the primary endpoint, Arm A showed some objective tumor responses and beneficial immunologic changes in long-term survivors, such as increased CD8+ T cells, suggesting potential for immune modulation even if overall survival was similar to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer. Tsujikawa, T., Crocenzi, T., Durham, JN., et al.[2023]

High levels of CSF-1R in pancreatic cancer patients treated with the GVAX vaccine were linked to a poorer survival rate due to increased myeloid cell infiltration, which can suppress immune responses.

Combining anti-CSF-1R therapy with GVAX and anti-PD-1 significantly improved survival in a mouse model of pancreatic cancer, suggesting that this combination may enhance the activation of T-cells and improve anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting myeloid-inflamed tumor with anti-CSF-1R antibody expands CD137+ effector T-cells in the murine model of pancreatic cancer. Saung, MT., Muth, S., Ding, D., et al.[2019]

In a phase II study involving 82 patients with metastatic pancreatic ductal adenocarcinoma, the combination of GVAX and ipilimumab did not improve overall survival compared to continuing standard chemotherapy (FOLFIRINOX), with median survival times of 9.38 months versus 14.7 months, respectively.

Despite the lack of survival benefit, the GVAX and ipilimumab treatment did show some immune response effects, such as promoting T-cell differentiation and increasing M1 macrophages in the tumor, suggesting potential biological activity worth exploring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Allogeneic GM-CSF-Transfected Pancreatic Tumor Vaccine (GVAX) with Ipilimumab as Maintenance Treatment for Metastatic Pancreatic Cancer. Wu, AA., Bever, KM., Ho, WJ., et al.[2022]

The combination of GVAX vaccine with nivolumab and urelumab significantly increased the number of activated CD8+ CD137+ T cells in tumors, indicating a robust immune response, and was well-tolerated by patients.

While the median disease-free and overall survival rates were numerically improved with the combination therapy compared to other treatment arms, the results were not statistically significant, suggesting that further studies are needed to confirm these promising findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma. Heumann, T., Judkins, C., Li, K., et al.[2023]

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Anti-IL-8 antibody activates myeloid cells and potentiates ... This study suggested that anti-IL-8 antibodies potentiate PD-1 blockade and informed the design of an ongoing clinical trial.

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BMS-986253 Plus Nivolumab/Ipilimumab Fails to Boost ... BMS-986253 plus nivolumab/ipilimumab failed to improve responses or PFS in advanced melanoma after progression on or after a checkpoint inhibitor.

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