A Study of Zolbetuximab With Chemotherapy in Adults With Pancreatic Cancer

NCT06396091 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 8951-CL-5203
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic cancer is difficult to diagnose early. By the time people have been diagnosed, the cancer has usually spread to other parts of the body (metastatic). The standard treatment is chemotherapy, but other treatments are needed to improve outcomes in people with pancreatic cancer. In this study, zolbetuximab will be given together with chemotherapy to people with pancreatic cancer. Zolbetuximab attaches to a protein called CLDN18.2 found at high levels on the surface of the cancer tumor. This switches on the immune system to attack the tumor. Adults 18 years or older with metastatic pancreatic cancer who have not previously had chemotherapy can take part in the study. There are 2 main aims of this study:

• To check the safety of zolbetuximab, when given with chemotherapy in people with metastatic pancreatic cancer
• To check if people could cope with (tolerate) any medical problems during the study This is an open-label study. This means people in the study and the study doctors will know that people will receive zolbetuximab with chemotherapy. Different small groups will receive lower to higher doses of zolbetuximab with chemotherapy. Zolbetuximab and chemotherapy will be given through a vein. This is called an infusion. People will receive zolbetuximab on the first day they receive chemotherapy. This will happen every 14 days in a 28-day cycle. People will receive zolbetuximab and chemotherapy in the study clinic and at home. Also, doctors will check for any medical problems. People will also have a health check including blood tests. On some visits they will also have scans to check for any changes in their cancer. People will visit the study clinic about 7 days after they stop treatment. They will be asked about any medical problems and will have a health check including blood tests. After this, people will have several more visits to the study clinic for health checks. The number of visits and checks done at each visit will depend on the health of each person and whether they complete their treatment or not.

Conditions

Metastatic Pancreatic Adenocarcinoma

Keywords

CLDN18.2 positive metastatic pancreatic adenocarcinoma; mFOLFIRINOX; Claudin 18.2

Outcome Measures

Primary Outcomes (6)

• Incidence of Dose Limiting Toxicities (DLT)

  A DLT will be defined as any event meeting the DLT criteria occurring during the DLT assessment period that is related to zolbetuximab.

  Up to 28 days

• Safety assessed by Adverse Events (AEs)

  An AE is any untoward medical occurrence in a patient or clinical study participant temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures.

  Up to 16 months

• Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant laboratory values.

  Up to 16 months

• Number of participants with vital sign abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant vital sign values.

  Up to 16 months

• Number of participants with electrocardiograms (ECG) abnormalities and or adverse events

  Number of participants with potentially clinically significant ECG values.

  Up to 16 months

• Number of participants at each grade of Eastern Cooperative Oncology Group (ECOG) performance status scores

  The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.

  Up to 15 months

Secondary Outcomes (7)

• Pharmacokinetics (PK) of zolbetuximab in serum: End of infusion concentrations

  Up to 1 month

• PK of zolbetuximab in serum: Concentration Immediately Prior to Dosing at multiple dosing (Ctrough)

  Up to 12 months

• Number of participants with positive antidrug antibodies (ADA) to zolbetuximab

  Up to 15 months

• Change from baseline in Cancer Antigen 19-9 (CA 19-9)

  Baseline up to 13 months

• Best Overall Response (BOR) Rate

  Up to 15 months

Study Arms (1)

zolbetuximab and mFOLFIRINOX

EXPERIMENTAL

Participants will receive 1 of 2 dose levels of zolbetuximab in combination with mFOLFIRINOX.

Drug: zolbetuximab; Drug: mFOLFIRINOX

Interventions

zolbetuximab DRUG

Zolbetuximab will be administered intravenously on day 1 then every two weeks.

Also known as: IMAB362

zolbetuximab and mFOLFIRINOX

mFOLFIRINOX DRUG

Modified oxaliplatin, leucovorin, irinotecan and fluorouracil (mFOLFIRINOX) will be administered intravenously within 2 days after administration of zolbetuximab.

zolbetuximab and mFOLFIRINOX

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (1)

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

MeSH Terms

Interventions

zolbetuximab

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: May 2, 2024
• Study Start: September 24, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: November 13, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)