Immunotherapy for Pancreatic Cancer

(KISIMA-02 Trial)

Recruiting at 22 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

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KISIMA-02 for individuals with pancreatic ductal adenocarcinoma (PDAC), a type of pancreatic cancer. The study will determine if KISIMA-02, either alone or with Ezabenlimab (an immunotherapy drug), can combat cancer. The trial will assess how much KISIMA-02 participants can safely tolerate and whether it can help prevent cancer recurrence. It is suitable for those diagnosed with PDAC who have completed some standard treatments and have stable health without disease progression. Participants will undergo regular check-ups to monitor their health and cancer status. As a Phase 1 trial, this research aims to understand how KISIMA-02 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research shows that KISIMA-02, which includes components ATP150, ATP152, and the viral vector VSV-GP154, is undergoing its first human trials. As a result, limited safety information is available. In this Phase 1 trial, the primary goal is to determine the maximum safe dosage for participants. This phase typically marks the initial step in human testing of a new treatment, so researchers are still learning about potential side effects and how the body processes the medicine.

Ezabenlimab, however, has undergone previous studies. Researchers are examining its effectiveness in treating various cancers, including pancreatic cancer. Some studies have shown that patients tolerate it well. However, like all treatments, it can cause side effects, which doctors monitor closely.

In summary, while KISIMA-02 is new and lacks detailed safety information, ezabenlimab has demonstrated manageable safety levels in earlier research. Trial participants will receive regular monitoring to ensure their safety and to identify any potential health issues caused by the treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they offer innovative approaches that differ from traditional chemotherapy and radiation. ATP150 and ATP152 are promising because they harness the power of the immune system, potentially leading to more targeted attacks on cancer cells with fewer side effects. Ezabenlimab, an immune checkpoint inhibitor, works by unleashing the immune system to recognize and destroy cancer cells more effectively, which could improve responses in patients who don't benefit from conventional treatments. VSV-GP154, a novel oncolytic virus, is designed to infect and kill cancer cells directly while also stimulating an immune response against the tumor. These treatments represent a shift towards more personalized and potentially more effective cancer therapies.

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

Research has shown that treatments like ATP150 and ATP152, which participants in this trial may receive, offer hope for fighting pancreatic cancer. These new vaccines use proteins to help the body's immune system combat cancer cells. Although ATP150 and ATP152 are still being tested in humans, early studies suggest these vaccines can enhance the immune system's ability to target tumors. Another treatment option in this trial, Ezabenlimab, helps the immune system recognize and attack cancer cells more effectively. While it's still early, these treatments aim to improve outcomes for pancreatic cancer, which remains very difficult to treat. ^{1 5 6 7 8}

Who Is on the Research Team?

Paul Oberstein, MD

Principal Investigator

NYU Langone Health

Shubham Pant, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 previously used immunotherapy treatments.

I have been diagnosed with an immune system disorder.

I am still recovering from pancreatic cancer surgery.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Cohort C Treatment Experimental Treatment 5 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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

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A Study to Evaluate ATP150/ATP152/ATP162, VSV-GP154 ... This is an open-label, phase 1b study to evaluate the safety, tolerability, immunogenicity and preliminary efficacy of a heterologous prime-boost vaccine ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12528555/

Emerging therapeutic advancements in pancreatic cancer Pancreatic cancer has significantly high mortality rate of approximately 90% and a dismal survival rate of 5 years in ~ 15–25% of patients who ...

3. withpower.com withpower.com/trial/phase-1-adenocarcinoma-2-2023-2f87d

Immunotherapy for Pancreatic Cancer (KISIMA-02 Trial) What data supports the effectiveness of the treatment ATP150, ATP152, Ezabenlimab, and VSV-GP154 for pancreatic cancer? Research shows that immunotherapy, ...

4. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1369136/full

Targeting KRAS mutations in pancreatic cancer The median PFS was 4.0 months (95% CI 2.8–5.6) with a median overall survival (OS) of 6.9 months (95% CI 5.0–9.1) (80) (Table 1). Table 1. Response to single ...

5. mdpi.com mdpi.com/2072-6694/17/14/2356

Cancer Vaccination and Immune-Based Approaches in ... Despite advances in therapy, in the U.S., the 5-year survival remains poor at around 13% across all stages and only 3% for metastatic disease [1]. Surgery with ...

6. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/inoncology/our-pipeline/kisima-cancer-vaccine

KISIMA® cancer vaccine | InOncology Efficacy and safety have not been established and there is no guarantee that they will become commercially available for the uses under investigation. Mechanism ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11428787/

The Road Ahead in Pancreatic Cancer: Emerging Trends and ... This trial aims to explore the safety, pharmacokinetics, and overall efficacy of AZD0171 in combination with durvalumab and chemotherapies (gemcitabine and nab- ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03866

A Study to Evaluate ATP150/ATP152/ATP162, VSV-GP154 ... This study is open to adult with Pancreatic Ductal Adenocarcinoma (PDAC). The purpose of this study is to find out whether a medicine called KISIMA-02 can ...