Pancreatic CancerPhase 1NCT06205849
Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer
A Phase 1 study testing IRE + intratumoral mitazalimab (CD40 antibody) injection and NanoKnife in people with Pancreatic Cancer, run by University of California, San Diego at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- IRE + intratumoral mitazalimab (CD40 antibody) injection and NanoKnife
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2024to Aug 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 23Show fewer
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UCSD Moores Cancer Center
La Jolla, California, 92093
John Bienvenida, (858) 822-4907, jbienvenida@health.ucsd.edu
About this study
Official title: Phase 1 Clinical Trial of Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer
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.
Read the detailed description
Irreversible electroporation (IRE) is a form of non-thermal ablation (tissue destruction) that is being used to treat locally advanced pancreatic cancers. Locally advanced pancreatic cancers are tumors that have not spread (metastasized to distant locations) but cannot be surgically resected. There is evidence that IRE can help to generate anti-tumor immune responses by releasing tumor antigens in the setting of inflammation. CD40 is an immune receptor that helps to stimulate antigen presentation to the immune system. Preclinical data from the PI's laboratory have shown that combination of IRE with an antibody that stimulates the CD40 receptor improves responses to IRE and inhibits metastatic tumor growth.
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
- Being tested
- IRE + intratumoral mitazalimab (CD40 antibody) injection, NanoKnife
- Keywords
- Irreversible electroporation (IRE), NanoKnife, immunotherapy, CD40, Locally advanced pancreatic cancer
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IRE + intratumoral mitazalimab (CD40 antibody) injectionDrug
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.
NanoKnifeDevice
Also called Irreversible electroporation
Non-thermal tumor ablation using short pulses of high voltage electrical current delivered using 19-gauge needles placed via laparotomy using ultrasound guidance
| Study group | Role | What they receive |
|---|---|---|
| IRE + CD40 Antibody | Experimental | Not described Receives: Drug: IRE + intratumoral mitazalimab (CD40 antibody) injection; Device: NanoKnife |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (3)
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
Measured: 5 years
Overall survival
Overall survival (OS), defined as the time from the date of IRE and mitazalimab administration to death from any cause.
Measured: 5 years
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2024
- Study start17 Jul 2024
- Primary completionAug 2028 (estimated)
- Study completionAug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rebekah White, University of California, San Diego
- Investigators
- Rebekah R White, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06205849
- Sponsor's protocol ID
- 807630
- Other IDs
- 1R01CA282439
- Status last verified
- Jun 2026
- First submitted
- 4 Jan 2024
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
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.
PubMed 36634919Irenaeus 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.
PubMed 30664811
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Clinical Trial of Intra-tumoral Mitazalimab (CD40 Antibody) With Irreversible Electroporation (IRE) in Locally Advanced Pancreas Cancer
- ClinicalTrials.gov ID
- NCT06205849
- Acronym / sponsor ID
- 807630
- Conditions
- Pancreatic Cancer
- Keywords
- Irreversible electroporation (IRE), NanoKnife, immunotherapy, CD40, Locally advanced pancreatic cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- University of California, Los Angeles, National Cancer Institute (NCI)
- Study start
- 17 Jul 2024 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2030 (estimated)
- First posted
- 16 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Irreversible electroporation (IRE) is a form of non-thermal ablation (tissue destruction) that is being used to treat locally advanced pancreatic cancers. Locally advanced pancreatic cancers are tumors that have not spread (metastasized to distant locations) but cannot be surgically resected. There is evidence that IRE can help to generate anti-tumor immune responses by releasing tumor antigens in the setting of inflammation. CD40 is an immune receptor that helps to stimulate antigen presentation to the immune system. Preclinical data from the PI's laboratory have shown that combination of IRE with an antibody that stimulates the CD40 receptor improves responses to IRE and inhibits metastatic tumor growth.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| IRE + CD40 Antibody | Experimental | Drug: IRE + intratumoral mitazalimab (CD40 antibody) injection, Device: NanoKnife |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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:
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IRE + intratumoral mitazalimab (CD40 antibody) injectionSurgical 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. | Drug | IRE + CD40 Antibody |
| NanoKnifeAlso: Irreversible electroporationNon-thermal tumor ablation using short pulses of high voltage electrical current delivered using 19-gauge needles placed via laparotomy using ultrasound guidance | Device | IRE + CD40 Antibody |
Primary outcome
Safety and tolerability
Time frame: 12 weeks
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.
3 secondary outcomes
Progression-free survival
Time frame: 5 years
Overall survival
Time frame: 5 years
Systemic immune effects
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Background: PubMed 36634919Shankara 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.
- Background: PubMed 30664811Irenaeus 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rebekah R White, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IRE + intratumoral mitazalimab (CD40 antibody) injection and NanoKnife in people with Pancreatic Cancer, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shakeela Dad (858-822-5376, sdad@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06205849, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.