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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest and most effective dose of a new treatment combination for patients with surgically removable pancreatic cancer. The study compares two treatment groups: one receiving a vaccine called GVAX and the other receiving a vaccine called mKRASvax, both combined with the drugs AGEN2373 and balstilimab. The researchers seek to evaluate the effectiveness of each treatment and ensure participant safety. Suitable candidates have newly diagnosed pancreatic cancer that can be surgically removed and are willing to undergo a biopsy. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in pancreatic cancer treatment.

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.

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

Earlier studies have shown that GVAX is mostly safe for patients with pancreatic cancer, causing only minor side effects while extending patients' lives. Similarly, research on mKRASvax indicates it is generally safe and aids the immune system in fighting cancer, with most patients experiencing few problems.

Balstilimab and AGEN2373 are newer treatments currently under testing. This trial is in the early stages, so limited safety information is available. However, early trials typically focus on ensuring treatment safety, with major side effects closely monitored and managed.

Overall, the treatments in this trial have demonstrated promising safety results in earlier research, but ongoing studies are crucial to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pancreatic cancer, which often rely on chemotherapy, the investigational treatments GVAX and mKRASvax offer a novel approach by engaging the body's own immune system. GVAX is a cancer vaccine designed to stimulate the immune response against tumor cells, while mKRASvax specifically targets mutations in the KRAS gene, a common driver in pancreatic cancer, using a peptide-based vaccine. Researchers are excited about these treatments because they represent a shift from traditional methods, potentially offering more targeted and personalized cancer therapy options with the hope of improved patient outcomes.

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

Research has shown that GVAX, a vaccine for pancreatic cancer, yields promising results in aiding the immune system to combat this cancer. Some studies have found that GVAX, when combined with other treatments, may extend patients' lives and improve treatment responses. In this trial, participants in one arm will receive GVAX alongside AGEN2373, Balstilimab, and Cyclophosphamide.

Another vaccine, mKRASvax, targets specific changes in the KRAS gene associated with pancreatic cancer. Early findings suggest it can trigger a strong immune response and might extend patients' lives. Participants in another arm of this trial will receive mKRASvax with AGEN2373 and Balstilimab. Both vaccines are being tested with other therapies to determine if they work better together. These early results are hopeful, but further research is needed to confirm their effectiveness. ^{2 3 5 6 7}

Who Is on the Research Team?

Eric Christenson, MD

Principal Investigator

SKCCC • Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7376746/

Results from a Phase IIb, Randomized, Multicenter Study of ... A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating ...

2. hopkinsmedicine.org hopkinsmedicine.org/news/newsroom/news-releases/2023/07/pancreatic-cancer-vaccine-plus-immunotherapy-and-antibody-spark-immune-system-response-in-pancreatic-cancers

Pancreatic Cancer Vaccine Plus Immunotherapy and ... A three-pronged combination immunotherapy treatment consisting of the pancreatic cancer vaccine GVAX, the immune checkpoint therapy nivolumab and urelemab, an ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01417000

Study Details | NCT01417000 | Safety and Efficacy of ... Study Overview​​ Test the safety, immune response and efficacy of GVAX pancreas vaccine (with cyclophosphamide) and CRS-207 compared to GVAX pancreas vaccine ( ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16309

Overall survival (OS) and pathologic response rate from a ... Overall survival (OS) and pathologic response rate from a phase II clinical trial of neoadjuvant GVAX pancreas vaccine (with cyclophosphamide) ...

5. msjonline.org msjonline.org/index.php/ijrms/article/download/14678/9362/69068

GVAX vaccine as a treatment for pancreatic cancer While these combinations demonstrated promising immunological effects and improved clinical outcomes in some cases, the overall survival benefit ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25584002/

Safety and survival with GVAX pancreas prime and ... - PubMed Heterologous prime/boost with Cy/GVAX and CRS-207 extended survival for patients with pancreatic cancer, with minimal toxicity.

7. mayo.edu mayo.edu/research/clinical-trials/cls-20143576

Safety and Efficacy of Combination Listeria/GVAX ... About this study. Test the safety, immune response and efficacy of GVAX pancreas vaccine (with cyclophosphamide) and CRS-207 compared to chemotherapy or ...