Using a CD40 antibody with electroporation to treat advanced pancreatic cancer
Phase 1 Clinical Trial of Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer
This study is testing a new way to treat advanced pancreatic cancer by injecting a special antibody directly into tumors during surgery to see if it helps the immune system fight the cancer better.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of California, San Diego Academic / other |
| Drugs / interventions | mitazalimab, chemotherapy, radiation, prednisone, immunotherapy |
| Locations | 1 site (La Jolla, California) |
| Trial ID | NCT06205849 on ClinicalTrials.gov |
What this trial studies
This phase I study investigates the use of mitazalimab, an agonistic CD40 antibody, injected directly into tumors during irreversible electroporation (IRE) surgery for patients with locally advanced pancreatic cancer. The approach aims to enhance the immune response against the tumor while minimizing systemic side effects associated with traditional immunotherapy. By delivering the antibody intratumorally, the study seeks to improve the effectiveness of IRE and reduce the risk of cancer recurrence. The study will assess the safety and immune response generated by this combination treatment.
Who should consider this trial
Good fit: Ideal candidates are adults over 18 with histologically confirmed locally advanced pancreatic ductal adenocarcinoma that cannot be surgically resected.
Not a fit: Patients with metastatic pancreatic cancer or those whose tumors are amenable to surgical resection may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a more effective and targeted approach to managing locally advanced pancreatic cancer.
How similar studies have performed: While the combination of IRE and immunotherapy is a novel approach, preclinical data suggests potential efficacy, though clinical success in similar studies is still being evaluated.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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) * Serum total bilirubin ≤ 1.5 X ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN * A minimum of 4 months of one of the chemotherapy regimens preferred by the NCCN for good performance status patients (currently modified FOLFIRINOX, gemcitabine + albumin-bound paclitaxel, or NALIRIFOX) * High quality imaging triphasic CT scan contrast-enhanced dynamic MRI of abdomen and either contrast-enhanced or non-contrast CT of chest and pelvis that demonstrate no evidence of metastatic disease within 30 days of enrollment * FDG-PET imaging (skullbase-midthigh) at any timepoint between diagnosis and study intervention to determine whether tumor is PET-avid and evaluate for extra-pancreatic metastatic disease, as suggested by NCCN guidelines for high-risk patients. * Tumor amenable to "in situ" (complete) ablation with maximum primary tumor dimension \< 4.0 cm * For participants able to become pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method until the study intervention and for an additional 1 month after the study intervention. * For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner for 1 month after study intervention. Exclusion Criteria: * 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.
Where this trial is running
La Jolla, California
- UCSD Moores Cancer Center — La Jolla, California, United States (Recruiting)
Study contacts
- Principal investigator: Rebekah R White, MD — University of California, San Diego
- Study coordinator: Shakeela Dad
- Email: sdad@health.ucsd.edu
- Phone: 858-822-5376
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.