Zolbetuximab combined with chemotherapy for metastatic pancreatic cancer

A Phase 1 Open-label Study to Assess the Safety and Tolerability of Zolbetuximab (IMAB362) in Combination With Chemotherapy (mFOLFIRINOX) in Participants With CLDN18.2 Positive Metastatic Pancreatic Adenocarcinoma

This study is testing if adding a new drug called zolbetuximab to standard chemotherapy can help adults with metastatic pancreatic cancer feel better and handle treatment side effects.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Astellas Pharma Inc (Industry-sponsored)
• Drugs / interventions: zolbetuximab, chemotherapy, radiation, prednisone
• Locations: 7 sites (Fullerton, California and 6 other locations)
• Trial ID: NCT06396091 on ClinicalTrials.gov

What this trial studies

This study investigates the use of zolbetuximab, an antibody targeting the CLDN18.2 protein, in combination with the chemotherapy regimen mFOLFIRINOX for adults with metastatic pancreatic adenocarcinoma. The primary goals are to assess the safety of this combination treatment and to evaluate how well patients tolerate any associated medical issues. Participants must be adults aged 18 or older who have not previously received chemotherapy for their metastatic pancreatic cancer. The study is open-label, meaning both participants and researchers are aware of the treatment being administered.

Who should consider this trial

Good fit: Ideal candidates are adults 18 years or older with untreated metastatic pancreatic adenocarcinoma that has not been previously treated with chemotherapy.

Not a fit: Patients who have previously received chemotherapy for their metastatic pancreatic cancer or those whose disease has progressed on prior mFOLFIRINOX treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with metastatic pancreatic cancer by enhancing the effectiveness of chemotherapy.

How similar studies have performed: While the approach of combining zolbetuximab with chemotherapy is innovative, similar studies targeting CLDN18.2 in other cancers have shown promise, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

* Participant has histologically or cytologically confirmed adenocarcinoma of pancreas.
* Participant must have metastatic pancreatic adenocarcinoma that has not been previously treated with chemotherapy:

  * Prior treatment with 5-fluorouracil or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed (if there is lingering toxicity, then the sponsor should be consulted).
  * If a participant received neoadjuvant/adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the neoadjuvant/adjuvant therapy.
  * Participant whose disease progressed on prior treatment with mFOLFIRINOX are not eligible.
* Participant has a measurable lesion(s) on at least 1 metastatic site based on RECIST v1.1 within 28 days prior to enrollment. For participants with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
* Participant's tumor is CLDN18.2 positive, defined as ≥ 75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining as determined by central immunohistochemistry testing.
* Female subject is not pregnant and at least 1 of the following conditions apply:

  * Not a woman of childbearing potential (WOCBP)
  * WOCBP who has a negative urine or serum pregnancy test at screening or within 48 hours prior to day 1; and agrees to follow the contraceptive guidance from the time of informed consent through through 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study interventional drugs.
* Female participant must not be breastfeeding or lactating starting at screening and throughout the treatment period and for 6 months after the final study intervention administration.
* Female participant must not donate ova starting at first administration of study intervention and throughout the treatment period and for 6 months after the final study intervention administration.
* A male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 6 months after final study intervention administration.
* A male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the treatment period and for 6 months after final study intervention administration.
* A male participant must not donate sperm during the treatment period and for 6 months after final study intervention administration.
* Participant agrees not to participate in another interventional study while receiving study intervention in the present study/participating in the present study.
* Participant has ECOG performance status 0 or 1.
* Participant has predicted life expectancy ≥ 12 weeks.
* Participant must meet all of the following criteria based on the laboratory tests collected within 14 days prior to enrollment. In case of multiple laboratory data within this period, the most recent data should be used.
* Participant must meet all of criteria based on laboratory tests during screening period.

Exclusion Criteria:

* Participant has prior severe allergic reaction; suspected, known immediate or delayed hypersensitivity; or intolerance or contraindication to known ingredients of zolbetuximab or other monoclonal antibody, including humanized or chimeric antibodies.
* Participant has prior severe allergic reaction; suspected, known immediate or delayed hypersensitivity; or intolerance or contraindication to any component of mFOLFIRINOX.
* Participant has known dihydropyrimidine dehydrogenase (DPD) deficiency.
* Participant has a known history of a positive test for human immunodeficiency virus infection or known active hepatitis B (positive HBs Ag) or hepatitis C infection.

  * For participants who are negative for hepatitis B surface antigen, but hepatitis B core antibody positive, a hepatitis B virus deoxyribonucleic acid test will be performed and if positive, the participant will be excluded.
  * Participants with positive hepatitis C serology but negative hepatitis C virus ribonucleic acid test results are eligible.
  * Participants treated for hepatitis C with undetectable viral load results are eligible.
* Participant has a history of interstitial pneumonia or pulmonary fibrosis.
* Participant has pleural effusion or ascites ≥ Grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
* Participant has an active autoimmune disease that has required systemic treatment in the past 3 months prior to enrollment.
* Participant has active infection requiring systemic therapy that has not completely resolved within 7 days prior to enrollment.
* Participant has significant cardiovascular disease, including:

  * Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting,coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to enrollment;
  * History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or torsades de pointes);
  * QT interval corrected for heart rate (QTc) \> 450 msec for male participants; QTc interval \> 470 msec for female participants;
  * Cardiac arrhythmias requiring anti-arrhythmic medications (Participants with rate-controlled atrial fibrillation for \> 1 month prior to enrollment are eligible).
* Participant has a history of central nervous system metastases and/or carcinomatous meningitis from pancreatic adenocarcinoma.
* Participant has known peripheral sensory neuropathy ≥ Grade 2 per CTCAE v5.0 unless the absence of deep tendon reflexes is the sole neurological abnormality.
* Participant has had diarrhea within 24 hours prior to enrollment.
* Participant has had a major surgical procedure ≤ 28 days prior to enrollment.
* Participant without complete recovery from a major surgical procedure ≤ 14 days prior to enrollment.
* Participant has a psychiatric illness or social situations that would preclude study compliance.
* Participant has another malignancy for which treatment is required.
* Participant has any concurrent disease, infection or co-morbid condition that interferes with the ability of the participant to participate in the study, which places the participant at undue risk or complicates the interpretation of data.
* Participant has received radiotherapy for metastatic pancreatic adenocarcinoma unless the radiotherapy was completed \> 14 days prior to enrollment and has recovered from any related toxicity.
* Participant has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to enrollment.
* Participant using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use is allowed.
* Participant has a present or previous history of participation in a study of the study intervention.
* Participant has a previous history of investigational study intervention administration.
* Participant uses strong inhibitors or inducers of CYP3A or UGT1A1 when using irinotecan.
* Participant has received any investigational therapy within 28 days prior to screening.
* Participant has any condition which makes the participant unsuitable for study participation.

Where this trial is running

Fullerton, California and 6 other locations

• Providence Medical Foundation — Fullerton, California, United States (Recruiting)
• Johns Hopkins Hospital — Washington, District of Columbia, United States (Recruiting)
• Norton Cancer Institute — Louisville, Kentucky, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• Virginia Mason Medical Center — Seattle, Washington, United States (Recruiting)
• MultiCare Deaconess & Blood Specialty Center — Spokane, Washington, United States (Recruiting)
• Multicare Health System Research — Tacoma, Washington, United States (Recruiting)

Study contacts

• Study coordinator: Astellas Pharma Global Development, Inc.

Conditions Metastatic Pancreatic Adenocarcinoma; CLDN18.2 positive metastatic pancreatic adenocarcinoma; mFOLFIRINOX; Claudin 18.2