# Irreversible Electroporation (IRE) Combined with CD40 Agonism as In Situ Vaccine Therapy for Pancreatic Cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $564,526

## Abstract

Up to 40% of patients with pancreatic cancer present with locally advanced pancreas cancer (LAPC), defined as
localized (non-metastatic) but unresectable. Treatment of this patient subset is a particularly glaring unmet need.
Irreversible electroporation (IRE) is a technique that is being used increasingly for ablation of persistent LAPC
after systemic therapy. Our group has demonstrated that IRE can function as an "in situ vaccine" by releasing
tumor neoantigens in the setting of inflammation and thereby promoting recognition of the tumor by the innate
immune system. CD40 is an immune receptor located on antigen-presenting cells that serves as a bridge
between the innate immune system and the host’s specific response to neoantigens (the adaptive immune
system). Using immunocompetent orthotopic mouse models of pancreatic cancer, we have shown that the
combination of IRE with local delivery of a CD40 agonistic antibody (CD40 Ab), can both improve the local effects
of IRE and decrease metastatic disease in the liver. ADC-1013 (mitazalimab) is a CD40 antibody that is currently
being studied in clinical trials as a systemic therapy for metastatic pancreatic cancer. It has also been delivered
by local (intratumoral) injection into a variety of superficial and deep tumors. Local (intratumoral) delivery is
appealing in that it has potential to be more effective while decreasing systemic side effects. Intratumoral injection
is also feasible at the time of IRE, which is generally performed via an open surgical approach. We hypothesize
that local delivery of a CD40 agonist at the time of IRE in patients with LAPC will augment the systemic immune
effects of IRE, enhance local disease control, and ultimately decrease distant recurrence. We propose to
conduct a phase I study of intratumoral mitazalimab injection at the time of surgical IRE to determine a
recommended Phase 2 dose and establish preliminary efficacy for future studies. In parallel, we will perform
correlative studies to determine if this combination can generate immune responses to neoantigens identified
using an unbiased bioinformatic analysis pipeline of tumor biopsies. Our multi-disciplinary team is uniquely
qualified to conduct the proposed studies. Dr. White is a surgical oncologist at UCSD with clinical expertise in
IRE and whose laboratory generated the preliminary data. Dr. Wainberg is a medical oncologist at UCLA with
expertise in immuno-oncology clinical trials and specifically CD40 agonists. Subjects will be recruited from all
five of the University of California Pancreatic Cancer Consortium centers. Dr. Schoenberger, at the La Jolla
Institute for Immunology, will assist with neoantigen identification from human tumor samples and measurement
of immune responses in post-treatment blood samples. We hypothesize that this novel approach to the treatment
of LAPC will prove to be safe, and result in progression-free survival superior to that of patients previously treated
with IRE alone. Wi...

## Key facts

- **NIH application ID:** 10931663
- **Project number:** 5R01CA282439-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Stephen Philip Schoenberger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $564,526
- **Award type:** 5
- **Project period:** 2023-09-19 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931663

## Citation

> US National Institutes of Health, RePORTER application 10931663, Irreversible Electroporation (IRE) Combined with CD40 Agonism as In Situ Vaccine Therapy for Pancreatic Cancer (5R01CA282439-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10931663. Licensed CC0.

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