Immunotherapy for Pancreatic Cancer

Recruiting at 16 trial locations

Overseen By AMAL Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amal Therapeutics

Must not be taking: Immunosuppressants, Tamoxifen

Disqualifiers: Other malignancy, Immunodeficiency, others

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

Compensation: Varies

Number of Visits: Unknown

85 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for pancreatic cancer using a special vaccine, a virus for delivery, and an immune-boosting drug. It aims to help the immune system better fight cancer in patients whose disease has spread, is locally advanced, or has been surgically removed. Vaccine therapy is being tested for many forms of cancer, including pancreatic cancer, with early trials showing safety and some increased survival.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must not have had chemotherapy, targeted therapy, or radiotherapy within 14 to 28 days before starting the trial, and you cannot use immunotherapy or certain other medications like Tamoxifen close to the trial's start.

What data supports the effectiveness of the treatment ATP150, ATP152, Ezabenlimab, and VSV-GP154 for pancreatic cancer?

Research shows that immunotherapy, including peptide vaccines and checkpoint blockade therapies, can activate immune cells to fight pancreatic cancer. For example, combining vaccines with other treatments has shown some promise in improving survival in pancreatic cancer patients. ^{1 2 3 4 5}

What makes the treatment ATP150, ATP152, Ezabenlimab, VSV-GP154 unique for pancreatic cancer?

This treatment is unique because it combines multiple immunotherapy components, including a therapeutic protein vaccine and checkpoint inhibitors, which aim to enhance the body's immune response against pancreatic cancer, a disease known for its resistance to standard treatments. ^{3 4 6 7 8}

Research Team

Shubham Pant, MD

Principal Investigator

M.D. Anderson Cancer Center

Paul Oberstein, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for pancreatic cancer patients with a specific mutation (KRAS G12D/G12V). They must have had surgery and chemotherapy, be in good physical condition, and not show signs of cancer returning. Those who've recently used certain drugs or treatments, have immune deficiencies or active autoimmune diseases, other recent cancers, or haven't recovered from surgery are excluded.

Inclusion Criteria

I had surgery to remove my cancer completely and underwent chemotherapy for at least 3 months.

My advanced cancer responded to or remained stable after 16 weeks of standard treatment.

My cancer has not grown or come back.

Exclusion Criteria

I have been diagnosed with an immune system disorder.

I am still recovering from pancreatic cancer surgery.

I have a blockage in my intestines.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive ATP150/ATP152 and VSV-GP154 treatment

Ongoing

Treatment Part B

Participants receive ATP150/ATP152, Ezabenlimab, and VSV-GP154 treatment with dose escalation

Ongoing

Treatment Part C

Participants receive ATP150/ATP152, Ezabenlimab, and VSV-GP154 treatment versus observational arm

Not started yet

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2.4 years

Treatment Details

Interventions

• ATP150
• ATP152
• Ezabenlimab
• VSV-GP154

Trial Overview The KISIMA-02 study tests an immunotherapy treatment on pancreatic cancer. It includes a protein vaccine (ATP150/152), a viral vector (VSV-GP154), and an immune checkpoint inhibitor (Ezabenlimab). The first part checks safety; the second compares treated patients to those only observed.

Participant Groups

Group I: Cohort C Treatment Experimental Treatment 4 Interventions

Group II: Cohort B Experimental Treatment 4 Interventions

Group III: Cohort A Experimental Treatment 3 Interventions

Group IV: Cohort C Observational Active Control 1 Intervention

Who Is Running the Clinical Trial?

Amal Therapeutics

Lead Sponsor

Trials

2

Recruited

180+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

In a murine model of metastatic pancreatic ductal adenocarcinoma (PDAC), combining an anti-CD137 agonist antibody with a GVAX cancer vaccine and anti-PD-1 therapy significantly improved survival rates, indicating a promising new treatment strategy.

The combination therapy enhanced T cell activation and increased the expression of costimulatory molecules, suggesting that targeting CD137 can effectively boost the immune response against PDAC, as supported by immunohistochemistry findings in human PDAC samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma. Muth, ST., Saung, MT., Blair, AB., et al.[2022]

Pancreatic ductal adenocarcinoma (PDAC) tissues showed significantly higher levels of VISTA expression compared to non-tumorous pancreatic tissues, and high VISTA levels in tumors were associated with reduced overall survival in patients.

Blocking VISTA in an orthotopic PDAC mouse model led to reduced tumor weights, suggesting that targeting VISTA could be a promising immunotherapy strategy for improving treatment outcomes in PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VISTA Ligation Reduces Antitumor T-Cell Activity in Pancreatic Cancer. Digomann, D., Strack, J., Heiduk, M., et al.[2023]

In a phase II study involving 83 patients with advanced pancreatic adenocarcinoma, the combination of survivin 2B peptide (SVN-2B) and interferon-β (IFNβ) did not significantly improve progression-free survival (PFS) compared to placebo, indicating limited efficacy in halting disease progression.

However, patients who received SVN-2B plus IFNβ showed a significant immunological response and better overall survival in subsequent treatments, suggesting that a longer vaccination protocol may provide survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA-A24-positive pancreatic adenocarcinoma. Shima, H., Tsurita, G., Wada, S., et al.[2023]

In pancreatic ductal adenocarcinoma (PDAC) associated with pancreatitis (ptPDAC), specific activation of type-I conventional dendritic cells (cDC1s) enhances the effectiveness of immune checkpoint blockade therapy (iCBT), leading to the activation of cytotoxic CD8+ T cells and significant tumor eradication.

Using PDAC antigen-loaded cDC1s as a vaccine can make previously immunotherapy-resistant PDAC tumors responsive to iCBT, suggesting a promising combination treatment strategy that could improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen-presenting type-I conventional dendritic cells facilitate curative checkpoint blockade immunotherapy in pancreatic cancer. Mahadevan, KK., Dyevoich, AM., Chen, Y., et al.[2023]

The combination of a Wilms' tumor gene 1 (WT1) vaccine with gemcitabine (GEM) showed a trend towards prolonged progression-free survival (PFS) in patients with advanced pancreatic ductal adenocarcinoma (PDAC), particularly in those with metastatic disease, where PFS was significantly improved (HR 0.51, P = 0.0017).

The treatment was well tolerated with no unexpected serious adverse events, and the presence of WT1-specific immune responses (measured by delayed-type hypersensitivity) correlated with better outcomes, suggesting that the vaccine may enhance the efficacy of gemcitabine in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study. Nishida, S., Ishikawa, T., Egawa, S., et al.[2022]

Pancreatic tumors are highly resistant to chemotherapy and are often diagnosed at advanced stages, leading to limited treatment options for patients.

Despite decades of research into vaccine therapies for pancreatic cancer, recent reviews indicate that none have successfully improved clinical outcomes, highlighting the ongoing challenges in developing effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis? Mizuguchi, T., Torigoe, T., Satomi, F., et al.[2023]

Pancreatic cancer is a highly lethal disease, ranking as the seventh leading cause of cancer-related deaths globally, highlighting the urgent need for more effective treatments.

Recent studies suggest that immunotherapy could be a promising approach for treating pancreatic cancer, with various preclinical and clinical trials showing encouraging results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status of Immunotherapy Treatments for Pancreatic Cancer. Jimenez-Luna, C., Prados, J., Ortiz, R., et al.[2018]

The multi-target vaccine composed of peptides from cancer-testis antigens and VEGFRs was well-tolerated in a Phase I trial with 9 patients suffering from advanced pancreatic cancer, showing no severe adverse events.

Four out of nine patients experienced clinical benefits, with median progression-free survival of 90 days and overall survival of 207 days, indicating potential efficacy of the vaccine in this difficult-to-treat population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological responses to a multi-peptide vaccine targeting cancer-testis antigens and VEGFRs in advanced pancreatic cancer patients. Okuyama, R., Aruga, A., Hatori, T., et al.[2021]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

CD137 agonist-based combination immunotherapy enhances activated, effector memory T cells and prolongs survival in pancreatic adenocarcinoma. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

VISTA Ligation Reduces Antitumor T-Cell Activity in Pancreatic Cancer. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA-A24-positive pancreatic adenocarcinoma. [2023]

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

Antigen-presenting type-I conventional dendritic cells facilitate curative checkpoint blockade immunotherapy in pancreatic cancer. [2023]

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

Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis? [2023]

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

Current Status of Immunotherapy Treatments for Pancreatic Cancer. [2018]

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

Immunological responses to a multi-peptide vaccine targeting cancer-testis antigens and VEGFRs in advanced pancreatic cancer patients. [2021]