Active, not recruiting
Phase 2
A Study of Zolbetuximab (IMAB362) in Adults With Pancreatic Cancer
Condition(s) studied
Pancreatic CancerMetastatic Pancreatic CancerMetastatic Pancreatic Adenocarcinoma
Investigational drug(s) / intervention(s)
zolbetuximabnab-paclitaxelgemcitabine
zolbetuximab: Administered as an intravenous infusion.
nab-paclitaxel: Administered as an intravenous infusion
gemcitabine: Administered as an intravenous infusion
Study summary
Zolbetuximab is being studied as a treatment for people with pancreatic cancer. Most people with pancreatic cancer have a protein called Claudin 18.2 (CLDN18.2) in their tumor. Zolbetuximab is thought to work by attaching to CLDN 18.2 in their tumor. This switches on the body's immune system to attack the tumor. Zolbetuximab is a potential treatment for people with pancreatic cancer.
There is an unmet medical need to treat people with pancreatic cancer. This study will help find the dose of zolbetuximab to be used with chemotherapy and provide more information on this treatment in adults with metastatic pancreatic cancer. The study is currently ongoing globally. People in this study will be treated with either zolbetuximab and chemotherapy or chemotherapy by itself.
The study's main aims are to find a suitable dose of zolbetuximab to be used with chemotherapy in the second part of this study, to check if zolbetuximab and chemotherapy compared to chemotherapy by itself can improve the survival of people with pancreatic cancer, and to check the safety of zolbetuximab when given with chemotherapy and how well people cope with medical problems during the study.
Adults with metastatic pancreatic cancer can take part. Their cancer is metastatic, has the CLDN18.2 marker in a tumor sample and has not previously been treated with chemotherapy. Metastatic means the cancer has spread to other parts of the body. People cannot take part are if they have recently had radiotherapy and have not recovered, need to take medicines to suppress their immune system, have history of nervous system metastases from their pancreatic cancer, or they have other active cancers that need treatment. People who have a specific heart condition or infections also cannot take part.
This study will be in 2 parts. Part 1 is called the Safety Lead-in Phase. Groups of people will receive 1 of 2 different doses of zolbetuximab: a lower dose or a higher dose, both together with chemotherapy. A medical expert panel will check the results and decide the dose to use in Part 2.
Part 2 is called the Randomization Phase. People will be put in 1 of 2 groups by chance and will be given different treatments either zolbetuximab and chemotherapy or chemotherapy by itself. The chance of receiving zolbetuximab and chemotherapy is twice as high as receiving chemotherapy by itself. In both parts of the study, zolbetuximab and chemotherapy or chemotherapy by itself will be given through a vein. This is called an infusion. Each treatment cycle is 4 weeks (28 days) long and people will have either 2 infusions of zolbetuximab and 3 infusions of chemotherapy or 3 infusions of chemotherapy by itself during each treatment cycle. People will visit the clinic on certain days during their treatment. The study doctors will check for any medical problems from zolbetuximab. Also, people in the study will have a health check including blood tests. On some visits they will also have scans to check for any changes in their cancer. Tumor samples will be taken before treatment if a previous sample is not available. People will have the option of giving a tumor sample after treatment has finished. People will visit the clinic after they stop treatment. They will be asked about any medical problems and will have a health check including blood tests. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.
Astellas is terminating the zolbetuximab pancreatic development program from Dec 2025 (following the final OS analysis in Oct 2025). Active subjects may remain on treatment if the investigator determines they are receiving benefit from it. The Survival follow-up period is no longer required.
Eligibility
Inclusion Criteria:
* A female subject is eligible to participate if she is not pregnant or lactating and at least 1 of the following conditions applies:
* Not a woman of childbearing potential (WOCBP) OR
* WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration.
* Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
* Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
* A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
* A male subject must not donate sperm during the treatment period and for at least 6 months after the final study drug administration.
* Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
* Subject agrees not to participate in other interventional studies while receiving study drug in present study.
* Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
* Subjects must have metastatic pancreatic adenocarcinoma that has not been previously treated with chemotherapy.
* Prior treatment with fluorouracil (5-FU) or GEM administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed
* If a subject received adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the adjuvant therapy.
* Subjects whose disease progressed on prior treatment with Nab-P and GEM are not eligible.
* Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1 within 28 days prior to randomization. For subjects 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.
* Subject's tumor sample has CLDN18.2 expression in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing
* Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Subject has predicted life expectancy ≥ 12 weeks.
* Subject must meet all of the following criteria based on the laboratory tests that will be collected within 14 days prior to randomization. In case of multiple laboratory data within this period, the most recent data should be used.
* Hemoglobin ≥ 9 g/dl (no transfusion within 14 days of start of study treatment)
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Platelets ≥ 100 x 10\^9/L
* Albumin ≥ 2.5 g/dL
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (≤ 5 x ULN if liver metastases are present)
* Estimated creatinine clearance ≥ 30 mL/min
* Prothrombin time/international normalized ratio (INR) and partial thromboplastin time ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
Exclusion Criteria:
* Subject has received other investigational treatment within 28 days prior to randomization.
* Subject has received radiotherapy for metastatic pancreatic adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
* Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. Subject 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 are allowed.
* Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibody, including humanized or chimeric antibodies.
* Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
* Subject has a known history of a positive test for human immunodeficiency virus infection or known active hepatitis B (positive HBs antigen \[Ag\]) or hepatitis C infection. NOTE: Screening for these infections should be conducted per local requirements.
1. For subjects who are negative for HBs Ag, but hepatitis B core antibody positive, a hepatitis B virus DNA test will be performed and if positive, the subject will be excluded.
2. Subjects with positive hepatitis C serology but negative hepatitis C virus RNA test results are eligible.
3. Subjects treated for hepatitis C with undetectable viral load results are eligible.
* Subject has a history of interstitial pneumonia or pulmonary fibrosis.
* Subject has pleural effusion or ascites ≥ Grade 3.
* Subject has an active autoimmune disease that has required systemic treatment in the past 3 months prior to randomization.
* Subject has active infection requiring systemic therapy that has not completely resolved per investigator judgment within 7 days prior to randomization.
* Subject 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 randomization;
* History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
* QTc interval \> 450 msec for male subjects; QTc interval \> 470 msec for female subjects;
* Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for \> 1 month prior to randomization.)
* Subject has a history of central nervous system metastases and/or carcinomatous meningitis from pancreatic adenocarcinoma.
* Subject has known peripheral sensory neuropathy ≥ Grade 2 unless the absence of deep tendon reflexes is the sole neurological abnormality.
* Subject has had a major surgical procedure ≤ 28 days prior to randomization.
* Subject without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
* Psychiatric illness or social situations that would preclude study compliance.
* Subject has another malignancy for which treatment is required.
* Subject has any concurrent disease, infection or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.
Primary outcome measure(s)
- Dose Limiting Toxicities (DLT) - (safety lead in) — Up to 28 days
Incidence of dose limiting toxicities.
- Overall Survival (OS) — Up to 79 months
OS is defined as the time from the date of randomization until the date of death from any cause.
- Safety assessed by Adverse Events (AEs) — From signing inform consent form until 90 days after the last dose of the study drug (Up to 82 months)
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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 a medicinal product.
- Safety assessed by incidence of serious adverse events (SAE) — From signing inform consent form until 90 days after the last dose of the study drug (Up to 82 months)
Adverse Event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.
- Safety assessed by incidence of treatment emergent adverse events (TEAE) — From first dose up to 30 days after last dose (Up to 80 months)
Treatment Emergent Adverse Event (TEAE) is defined as any AE which starts, or worsens, after the first dose of study drug through 30 days after the last dose of study drug.
- Number of participants with laboratory value abnormalities and/or adverse events (AEs) — From first dose up to 30 days after last dose (Up to 80 months)
Number of participants with potentially clinically significant laboratory values.
- Number of participants with vital sign abnormalities and /or adverse events (AEs) — From first dose up to 30 days after last dose (Up to 80 months)
Number of participants with potentially clinically significant vital sign values.
- Number of participants with electrocardiograms (ECG) abnormalities and or adverse events — From first dose up to 30 days after last dose (Up to 80 months)
12-lead ECGs will be recorded. Prior to the ECG, participants should rest in supine position for 10 minutes. ECGs will be read and assessed locally.
- Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events — From first dose up to 30 days after last dose (Up to 80 months)
Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.
Trial sites (136)
| Facility | City | Region | Status |
| St. Joseph Heritage Medical Group |
Fullerton |
California |
|
| TOI Clinical research |
Whittier |
California |
|
| Midstate Medical Center |
Meriden |
Connecticut |
|
| Lynn Cancer Institute |
Boca Raton |
Florida |
|
| Baptist Health |
Miami |
Florida |
|
| Cancer Treatment Centers of Atlanta |
Newnan |
Georgia |
|
| University of Illinois at Chicago |
Chicago |
Illinois |
|
| Norton Cancer Institute (NCI) |
Louisville |
Kentucky |
|
| Ochsner Health System |
New Orleans |
Louisiana |
|
| David C Pratt Cancer Center |
Creve Coeur |
Missouri |
|
| Memorial Sloan Kettering Basking Ridge |
Basking Ridge |
New Jersey |
|
| Memorial Sloan Kettering Bergen |
Montvale |
New Jersey |
|
| Roswell Park Cancer Institute |
Buffalo |
New York |
|
| Memorial Sloan Kettering Commack |
Commack |
New York |
|
| Memorial Sloan Kettering Westchester |
Harrison |
New York |
|
| Northwell Health Cancer Institute |
Lake Success |
New York |
|
| Memorial Sloan-Kettering Cancer Center |
New York |
New York |
|
| Memorial Sloan Kettering Nassau |
Uniondale |
New York |
|
| Novant Health Presbyterian Medical Center |
Charlotte |
North Carolina |
|
| Novant Health |
Winston-Salem |
North Carolina |
|
| Houston Methodist Hospital |
Houston |
Texas |
|
| Utah Cancer Specialists |
Salt Lake City |
Utah |
|
| MultiCare Regional Cancer Center - Gig Harbor |
Gig Harbor |
Washington |
|
| Vista Oncology |
Olympia |
Washington |
|
| Virginia Mason |
Seattle |
Washington |
|
| Site AU61008 |
Gosford |
New South Wales |
|
| Site AU61007 |
Wollongong |
New South Wales |
|
| Site AU61005 |
Fitzroy |
Victoria |
|
| Site AU61006 |
Warrnambool |
Victoria |
|
| Site BR55012 |
Porto Alegre |
Rio Grande do Sul |
|
| Site BR55009 |
Centro Passo Fundo |
Brazil |
|
| Site BR55008 |
Rio Grande |
Brazil |
|
| Site BR55004 |
Santa Catarina |
Brazil |
|
| Site BR55010 |
São Paulo |
Brazil |
|
| Site BR55011 |
São Paulo |
Brazil |
|
| Site CN86001 |
Beijing |
China |
|
| Site CN86008 |
Beijing |
China |
|
| Site CN86014 |
Beijing |
China |
|
| Site CN86026 |
Changchun |
China |
|
| Site CN86009 |
Chongqing |
China |
|
+ 96 more sites — see the full list on the official registry below.
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