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.
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Histologically/cytologically-confirmed pancreatic ductal adenocarcinoma (PDAC)
Persons, aged > 18 years of age, as PDAC is extremely rare in pediatric populations.
Pregnancy or lactation
Known allergic reactions to components of the mitazalimab solution (L-Histidine, trehalose, or polysorbate 20)
Fever > 38 degrees C within 14 days of study intervention
Treatment with another investigational drug or other intervention within 30 days of enrollment
Single group
IRE + intratumoral mitazalimab (CD40 antibody) injection
DrugSurgical IRE will be performed using the NanoKnife System with intraoperative ultrasound guidance via laparotomy under general anesthesia. Mitazalimab (CD40 antibody) will be administered 5 minutes after completion of IRE by slow injection into the center of the ablated zone using a small needle. Core needle biopsies of the tumor will be obtained immediately prior to IRE for identification of candidate tumor antigens. Peripheral blood will be obtained immediately prior to and 12 weeks after the study intervention for analysis of systemic immune effects.
NanoKnife
DeviceNon-thermal tumor ablation using short pulses of high voltage electrical current delivered using 19-gauge needles placed via laparotomy using ultrasound guidance
Safety and tolerability
Rates of dose-limiting toxicities (DLTs) and treatment-related adverse events (AEs). AE's will be graded by CTCAE v4, including grading for cytokine release syndrome. A DLT will be defined as any treatment emergent Grade 3 or higher AE that is potentially attributable to mitazalimab or the combination of IRE and mitazalimab. Exceptions will include AE's attributable to normal disease progression.
Progression-free survival
Progression-free survival (PFS), defined as the time from the date of IRE and mitazalimab administration to date of first observed disease progression or death from any cause
Overall survival
Overall survival (OS), defined as the time from the date of IRE and mitazalimab administration to death from any cause.
Systemic immune effects
Neoantigen-specific T-cell responses will be compared between peripheral blood samples obtained pre- and 12 weeks post-IRE using neoantigens identified from tumor biopsies.
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University of California, San Diego
Lead sponsor
University of California, Los Angeles
Collaborator
National Cancer Institute (NCI)
Collaborator
