Mitazalimab + IRE for Pancreatic Cancer

Overseen By Shakeela Dad

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Diego

Must be taking: FOLFIRINOX chemotherapy

Must not be taking: Immunosuppressive corticosteroids

Disqualifiers: Pregnancy, Auto-immune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications like corticosteroids at doses higher than 10 mg/day, you must stop them at least 2 weeks before the study treatment.

What data supports the effectiveness of the treatment Mitazalimab + IRE for Pancreatic Cancer?

Research shows that irreversible electroporation (IRE) can help the immune system fight pancreatic cancer by making the tumor environment less suppressive and allowing immune cells to attack the cancer more effectively. When combined with immune therapies, IRE has been shown to improve survival in animal models of pancreatic cancer. ^{1 2 3 4 5}

Is the combination of Mitazalimab and Irreversible Electroporation (IRE) safe for humans?

Irreversible Electroporation (IRE) has been studied for safety in combination with other treatments for pancreatic cancer, showing potential as a non-thermal method to treat tumors. However, immune-related adverse events (irAEs) are possible when combining IRE with immune therapies, which can affect various organs, including the pancreas, and may require careful management. ^{6 7 8 9 10}

How does the treatment Mitazalimab + IRE for pancreatic cancer differ from other treatments?

The treatment combines Mitazalimab, an immunotherapy drug, with irreversible electroporation (IRE), a non-thermal technique that uses electrical pulses to kill cancer cells without harming surrounding tissues. This combination aims to enhance the immune response against pancreatic cancer, offering a novel approach compared to traditional treatments that may not effectively target the immune system. ^{1 3 11 12 13}

What is the purpose of this trial?

This is a phase I study of an agonistic CD40 antibody (mitazalimab) injected intratumorally at the time of surgical IRE in patients with locally advanced pancreatic cancer. Intratumoral delivery has potential to be more effective than systemic (intravenous) delivery while decreasing the systemic side effects of immunotherapy. We hypothesize that local delivery of mitazalimab at the time of IRE in patients with locally advanced pancreatic cancer will be safe, augment the immune effects of IRE, and decrease the risk of recurrence.

Research Team

Rebekah R White, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for individuals with locally advanced pancreatic cancer who are eligible for a procedure called IRE. The study aims to test the safety and effectiveness of injecting a drug directly into the tumor during this procedure.

Inclusion Criteria

Provision of signed and dated informed consent form

I am over 18 years old.

My cancer is confirmed as pancreatic ductal adenocarcinoma.

Exclusion Criteria

I am not allergic to L-Histidine, trehalose, or polysorbate 20.

I have not had a fever over 38°C in the last 14 days.

I have had radiation therapy targeting my pancreas.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intratumoral mitazalimab (CD40 antibody) at the time of surgical IRE

12 weeks

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Regular follow-up visits

Treatment Details

Interventions

• Irreversible Electroporation (IRE)
• Mitazalimab

Trial Overview The trial is testing mitazalimab, an immune-stimulating antibody, given by direct injection into the tumor at the time of IRE surgery. It's compared with just having IRE (also known as NanoKnife), which uses electrical currents to destroy cancer cells.

Participant Groups

Group I: IRE + CD40 Antibody Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

Findings from Research

Irreversible electroporation (IRE) combined with nivolumab shows a promising safety profile, as no dose-limiting toxicities were observed in a phase 1b clinical trial involving 10 patients, with a median follow-up of 12 months.

The combination therapy resulted in a mean time to progression of 6.3 months and a median overall survival of 18.0 months, suggesting potential efficacy in treating locally advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b trial of concurrent immunotherapy and irreversible electroporation in the treatment of locally advanced pancreatic adenocarcinoma. O'Neill, C., Hayat, T., Hamm, J., et al.[2023]

Irreversible electroporation (IRE) effectively modifies the immunosuppressive tumor environment in pancreatic ductal adenocarcinoma (PDAC), enhancing the immune response without damaging the tumor's structural collagen.

Combining IRE with anti-PD1 immune checkpoint blockade leads to increased CD8+ T cell infiltration and significantly improves survival in a mouse model of PDAC, indicating a potential strategy to boost immunotherapy effectiveness in this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer. Zhao, J., Wen, X., Tian, L., et al.[2020]

Irreversible electroporation (IRE) demonstrated a high technical success rate of 99% in treating liver and pancreatic tumors, with significant improvements in complete tumor ablation rates from 65% in the first cohort to 87.76% in the second cohort for hepatic tumors.

IRE is considered a safe and effective treatment option for liver tumors that are not suitable for traditional thermal ablation, although its effectiveness for pancreatic tumors remains uncertain and needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of irreversible electroporation treatment in hepatobiliary and pancreatic tumours: a single-centre experience. Fang, C., Kibriya, N., Heaton, ND., et al.[2021]

In a study of 103 patients with locally advanced pancreatic cancer, those who received irreversible electroporation (IRE) combined with chemotherapy and PD-1/PD-L1 blockade (group A) had significantly better overall survival (23.6 months) and progression-free survival (18.2 months) compared to those who received IRE with chemotherapy alone (group B) with median survival of 19.4 months and 14.7 months, respectively.

The combination treatment not only improved survival outcomes but also demonstrated a robust immune response without increasing adverse events, indicating that adding PD-1/PD-L1 blockade to IRE and chemotherapy is a promising strategy for enhancing antitumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible electroporation combined with chemotherapy and PD-1/PD-L1 blockade enhanced antitumor immunity for locally advanced pancreatic cancer. Ma, Y., Xing, Y., Li, H., et al.[2023]

Irreversible electroporation (IRE) combined with chemotherapy showed improved overall survival (OS) in patients with unresectable pancreatic carcinoma, with median OS of 20.3 months for stage III patients receiving both treatments compared to 16.2 months for those receiving only IRE.

While IRE was generally well tolerated, with major complications occurring in only 7.4% of patients, it is important to note that severe complications were primarily associated with the open method of IRE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible electroporation combined with chemotherapy for unresectable pancreatic carcinoma: a prospective cohort study. Liu, S., Qin, Z., Xu, J., et al.[2022]

This study investigates the safety of combining irreversible electroporation (IRE) with immunotherapy drugs in 18 patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), aiming to enhance the immune response against tumors.

The combination of IRE with IMO-2125 and nivolumab may provide a novel treatment approach that could improve outcomes for mPDAC patients, who currently have limited effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible Electroporation and Nivolumab Combined with Intratumoral Administration of a Toll-Like Receptor Ligand, as a Means of In Vivo Vaccination for Metastatic Pancreatic Ductal Adenocarcinoma (PANFIRE-III). A Phase-I Study Protocol. Geboers, B., Timmer, FEF., Ruarus, AH., et al.[2021]

A case report demonstrated that combining irreversible electroporation (IRE) with pancreaticoduodenectomy (PD) in a patient with borderline resectable pancreatic carcinoma resulted in clear microscopic resection margins, which is crucial for better prognosis.

IRE is highlighted as a promising non-thermal treatment method that could enhance surgical outcomes for pancreatic cancer, warranting further investigation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible electroporation in borderline resectable pancreatic adenocarcinoma for margin accentuation. Papoulas, M., Abdul-Hamid, S., Peddu, P., et al.[2020]

In a case series of seven patients treated with immune checkpoint inhibitors (ICIs), two developed diabetic ketoacidosis (DKA) and five experienced pancreatitis, highlighting the potential for serious pancreatic adverse events associated with ICI therapy.

Pancreatitis was often asymptomatic and could be managed effectively by holding the ICI treatment and administering steroids, with some patients able to safely resume ICI therapy after recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic adverse events in patients treated with immune checkpoint inhibitors. Hana, C., Rehman, T., Park, K., et al.[2023]

Immune checkpoint inhibitors, such as those targeting CTLA-4, PD-1, and PD-L1, have become significant in cancer immunotherapy, showing promise in enhancing antitumor effects through both single-agent and combination therapies.

However, these therapies can lead to immune-related adverse events (irAEs), which vary in frequency and severity, highlighting the need for better understanding and management strategies for these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events From Immune Checkpoint Inhibitors. Marrone, KA., Ying, W., Naidoo, J.[2022]

Immune checkpoint inhibitors have shown promising results in improving survival rates for various advanced cancers, highlighting their efficacy as a novel anti-cancer therapy.

However, these treatments can lead to immune-related adverse events (irAEs) that affect multiple organs, necessitating careful management and collaboration between oncologists and gastroenterologists, especially since some irAEs can be severe and life-threatening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders as immune-related adverse events. Balducci, D., Quatraccioni, C., Benedetti, A., et al.[2022]

Irreversible electroporation (IRE) is a promising non-thermal treatment for liver metastases from pancreatic cancer, as demonstrated in a case where a 66-year-old patient achieved a complete response after IRE combined with arterial infusion chemotherapy and tegafur.

The patient has survived for over 12 months following this treatment, suggesting that the combination therapy may be effective and could serve as a potential reference for similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible electroporation for liver metastasis from pancreatic cancer: A case report. Ma, YY., Shi, JJ., Chen, JB., et al.[2020]

In a study using a mouse model of pancreatic cancer, complete ablation of tumors using irreversible electroporation (IRE) resulted in nonviable tumors, while partial ablation led to significant tumor recurrence and larger tumor sizes, indicating a more aggressive cancer biology.

Recurrent tumors after incomplete IRE showed increased expression of EpCAM, suggesting activation of cancer stem cells, which may contribute to their resistance to standard chemotherapy treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of irreversible electroporation in human pancreatic adenocarcinoma: advanced murine model. Philips, P., Li, Y., Li, S., et al.[2020]

Irreversible electroporation (IRE) is a promising treatment for locally advanced pancreatic cancer (LAPC) as it induces cell death through high-voltage electrical pulses while sparing surrounding critical structures, making it safer than traditional thermal ablation techniques.

IRE not only reduces tumor size but may also enhance the immune response against pancreatic cancer cells, suggesting potential benefits when combined with immunotherapy for treating tumors that are typically hard to target, like pancreatic ductal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irreversible Electroporation for Locally Advanced Pancreatic Cancer. Timmer, FEF., Geboers, B., Ruarus, AH., et al.[2020]

References

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

A phase 1b trial of concurrent immunotherapy and irreversible electroporation in the treatment of locally advanced pancreatic adenocarcinoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer. [2020]

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

Safety and efficacy of irreversible electroporation treatment in hepatobiliary and pancreatic tumours: a single-centre experience. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Irreversible electroporation combined with chemotherapy and PD-1/PD-L1 blockade enhanced antitumor immunity for locally advanced pancreatic cancer. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Irreversible electroporation combined with chemotherapy for unresectable pancreatic carcinoma: a prospective cohort study. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Irreversible Electroporation and Nivolumab Combined with Intratumoral Administration of a Toll-Like Receptor Ligand, as a Means of In Vivo Vaccination for Metastatic Pancreatic Ductal Adenocarcinoma (PANFIRE-III). A Phase-I Study Protocol. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Irreversible electroporation in borderline resectable pancreatic adenocarcinoma for margin accentuation. [2020]

8. Australia pubmed.ncbi.nlm.nih.gov

Pancreatic adverse events in patients treated with immune checkpoint inhibitors. [2023]

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

Immune-Related Adverse Events From Immune Checkpoint Inhibitors. [2022]

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

Gastrointestinal disorders as immune-related adverse events. [2022]

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

Irreversible electroporation for liver metastasis from pancreatic cancer: A case report. [2020]

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

Efficacy of irreversible electroporation in human pancreatic adenocarcinoma: advanced murine model. [2020]

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

Irreversible Electroporation for Locally Advanced Pancreatic Cancer. [2020]