GVAX vs mKRASvax for Pancreatic Cancer

Overseen By Colleen Apostol, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 1

38 Participants Needed

Trial Summary

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 14 days of starting the study drugs.

What data supports the effectiveness of the treatment GVAX vs mKRASvax for Pancreatic Cancer?

Research shows that combining GVAX with other immune therapies can increase the presence of certain immune cells in tumors and may improve survival in pancreatic cancer patients, although more studies are needed to confirm these findings. ^{1 2 3 4 5}

Is the GVAX vaccine safe for humans?

The GVAX vaccine has been tested in combination with other treatments for pancreatic cancer and is generally well-tolerated, with some patients experiencing immune-related side effects similar to other cancer immunotherapies. ^{1 2 3 4 5}

How does the GVAX vs mKRASvax treatment for pancreatic cancer differ from other treatments?

The GVAX treatment for pancreatic cancer is unique because it uses a vaccine approach that involves genetically modified pancreatic tumor cells to stimulate the immune system, often combined with other agents like cyclophosphamide to enhance its effects. This approach is different from standard chemotherapy as it aims to boost the body's own immune response to fight the cancer. ^{1 2 3 6 7}

What is the purpose of this trial?

The purpose of this study is to determine the optimal dose of AGEN2373 that is safe when given in combination with balstilimab and Pancreatic GVAX Whole Cell Vaccine and evaluate the safety and clinical activity of balstilimab and AGEN2373 in combination with GVAX (Arm 1) or mKRASvax (Arm 2) in surgically resectable pancreatic adenocarcinoma.

Research Team

Eric Christenson, MD

Principal Investigator

SKCCC • Johns Hopkins Medical Institution

Eligibility Criteria

This trial is for individuals with surgically removable pancreatic cancer. Participants must meet certain health standards, but specific inclusion criteria are not listed here. People with conditions that could interfere with the study or pose a risk to their safety based on the treatments being tested may be excluded.

Inclusion Criteria

I am fully active or can carry out light work.

My organ and bone marrow functions meet the required levels.

Women of childbearing potential (WOCBP) must have a negative serum pregnancy test

Exclusion Criteria

I have not received a live vaccine in the last 28 days.

History of severe hypersensitivity reaction to any monoclononal antibody

I have active tuberculosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive the study drugs (AGEN2373, balstilimab, and either GVAX or mKRASvax) prior to surgery to evaluate safety and clinical activity

2 weeks

Multiple visits for drug administration and monitoring

Surgery

Participants undergo surgical resection of pancreatic adenocarcinoma

1 day

1 visit (in-person)

Adjuvant Treatment

Participants receive additional study drugs post-surgery to further evaluate safety and clinical activity

13 weeks

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• AGEN2373
• Balstilimab
• GVAX
• mKRASvax

Trial Overview The study aims to find a safe dose of AGEN2373 and assess its effectiveness alongside balstilimab and either GVAX (Arm 1) or mKRASvax (Arm 2). These combinations are being tested as pre/post-surgery treatments for pancreatic cancer.

Participant Groups

Group I: Arm 2 - AGEN2373/Balstilimab/mKRASvax (1.8mg total peptides +0.5mg each poly-ICLC) Experimental Treatment 3 Interventions

Group II: Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX Experimental Treatment 4 Interventions

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Agenus Inc.

Industry Sponsor

Trials

58

Recruited

4,900+

Oncovir, Inc.

Industry Sponsor

Trials

25

Recruited

680+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

Findings from Research

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]

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]

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]

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]

References

1. England 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. [2023]

2. United States 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. [2022]

3. United States 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. [2023]

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

Durvalumab With or Without Tremelimumab for Patients With Metastatic Pancreatic Ductal Adenocarcinoma: A Phase 2 Randomized Clinical Trial. [2022]

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

Vaccination for Pancreatic Ductal Adenocarcinoma: A Hard Nut to Crack. [2019]

6. England 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. [2019]

7. United States 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. [2021]