Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer

NCT06205849 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: 8076301R01CA282439
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Cancer

Keywords

Irreversible electroporation (IRE); NanoKnife; immunotherapy; CD40; Locally advanced pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks

Secondary Outcomes (3)

• Progression-free survival

  5 years

• Overall survival

  5 years

• Systemic immune effects

  12 weeks

Study Arms (1)

IRE + CD40 Antibody

EXPERIMENTAL

Drug: IRE + intratumoral mitazalimab (CD40 antibody) injection; Device: NanoKnife

Interventions

IRE + intratumoral mitazalimab (CD40 antibody) injection DRUG

Surgical 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.

IRE + CD40 Antibody

NanoKnife DEVICE

Non-thermal tumor ablation using short pulses of high voltage electrical current delivered using 19-gauge needles placed via laparotomy using ultrasound guidance

Also known as: Irreversible electroporation

IRE + CD40 Antibody

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Locally advanced disease that is not amenable to surgical resection. Locally advanced PDAC cases will be identified per the definition developed by the Alliance for Clinical Trials in Oncology\[53\]. Per this definition, locally advanced PDAC is defined as presence of any one or more of the following on CT:
• Occlusion of the superior mesenteric vein (SMV) and/or portal vein (PV) that is not amenable to resection and venous reconstruction
• Interface between tumor and hepatic artery that is not amenable to resection and reconstruction
• Interface between the tumor and superior mesenteric artery (SMA) measuring \> 180º of the circumference of the vessel wall
• Interface between the tumor and celiac axis measuring \> 180º of the circumference of the vessel wall that is not amenable to resection
• ECOG Performance Status of 0-2
• Have adequate organ function per criteria below:
• Absolute neutrophil count (ANC) ≥ 1.5x109/L
• Platelets ≥ 100x109/L
• Hemoglobin ≥9 g/dL
• Serum creatinine ≤1.5 x ULN OR creatinine clearance ≥40 mL/min (as calculated by Modified Cockcroft-Gault formula)

You may not qualify if:

• 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
• Prior treatment with a CD40 antibody
• History of severe auto-immune disease
• The presence of metal fiducials or embolization coils within the tumor.
• Prior receipt of radiation therapy to the pancreas
• The presence of implanted metallic cardiac stimulation devices within the chest
• Uncontrolled cardiac arrhythmias that prevent synchronization of pulse delivery with the refractory period of the cardiac cycle
• Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks (14 days) before study treatment administration. Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤ 3 days) may be permitted.
• Any medical condition that precludes major abdominal surgery under general anesthesia
• Presence of distant metastatic disease (including positive peritoneal cytology) on staging laparoscopy and/or exploratory laparotomy at any timepoint.

Sponsors & Collaborators

• University of California, San Diego: lead
• University of California, Los Angeles: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

Related Publications (2)

• Shankara Narayanan JS, Hayashi T, Erdem S, McArdle S, Tiriac H, Ray P, Pu M, Mikulski Z, Miller A, Messer K, Carson D, Schoenberger S, White RR. Treatment of pancreatic cancer with irreversible electroporation and intratumoral CD40 antibody stimulates systemic immune responses that inhibit liver metastasis in an orthotopic model. J Immunother Cancer. 2023 Jan;11(1):e006133. doi: 10.1136/jitc-2022-006133.

  PMID: 36634919 BACKGROUND

• Irenaeus SMM, Nielsen D, Ellmark P, Yachnin J, Deronic A, Nilsson A, Norlen P, Veitonmaki N, Wennersten CS, Ullenhag GJ. First-in-human study with intratumoral administration of a CD40 agonistic antibody, ADC-1013, in advanced solid malignancies. Int J Cancer. 2019 Sep 1;145(5):1189-1199. doi: 10.1002/ijc.32141. Epub 2019 Mar 8.

  PMID: 30664811 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Electroporation; Injections

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Rebekah R White, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shakeela Dad

CONTACT

858-822-5376; sdad@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery

Model Details: Phase IA is a limited dose-escalation study. We will use an interval 3 + 3 dose escalation design, which allows rapid dose escalation and de-escalation while maintaining good overdose control. The starting intratumoral dose of mitazalimab in the first-in-human study was 22.5 µg/kg, but no serious adverse events were observed until the third dose level (200 µg/kg). As such, we conservatively propose to start at the second dose level (75 µg/kg) with a single dose escalation to 200 µg/kg, and de-escalation to 25 µg/kg if dose-limiting toxicities are encountered at 75 µg/kg. Phase IB will be an expansion cohort at the recommended phase II dose to establish preliminary evidence of efficacy.

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 16, 2024
• Study Start: June 25, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)