A Study of Zolbetuximab (IMAB362) in Adults With Pancreatic Cancer
A Phase 2, Open-Label, Randomized Study to Assess the Efficacy and Safety of Zolbetuximab (IMAB362) in Combination With Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects With Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma
4 other identifiers
interventional
393
13 countries
136
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 pancreatic-cancer
Started Mar 2019
Longer than P75 for phase_2 pancreatic-cancer
136 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 23, 2019
CompletedFirst Posted
Study publicly available on registry
January 25, 2019
CompletedStudy Start
First participant enrolled
March 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2026
March 12, 2026
March 1, 2026
7.5 years
January 23, 2019
March 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (9)
Dose Limiting Toxicities (DLT) - (safety lead in)
Incidence of dose limiting toxicities.
Up to 28 days
Overall Survival (OS)
OS is defined as the time from the date of randomization until the date of death from any cause.
Up to 65 months
Safety assessed by Adverse Events (AEs)
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.
Up to 65 months
Safety assessed by incidence of serious adverse events (SAE)
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.
Up to 65 months
Safety assessed by incidence of treatment emergent adverse events (TEAE)
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.
Up to 65 months
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Up to 65 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 65 months
Number of participants with electrocardiograms (ECG) abnormalities and or adverse events
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.
Up to 65 months
Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events
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.
Up to 65 months
Secondary Outcomes (32)
Progression Free Survival (PFS)
Up to 65 months
Objective Response Rate (ORR)
Up to 65 months
Number of anti-drug antibody (ADA) Positive Participants
Up to 65 months
Disease Control Rate (DCR)
Up to 65 months
Duration Of Response (DOR)
Up to 65 months
- +27 more secondary outcomes
Study Arms (2)
zolbetuximab +nab-paclitaxel + gemcitabine
EXPERIMENTALParticipants will be treated with zolbetuximab in combination with nab-paclitaxel and gemcitabine for the phase 1 portion of the study to establish the recommended dose of zolbetuximab for the phase 2 portion. In the phase 2 portion, the participants will be treated with zolbetuximab at dose determined by the phase 1 portion of the study in combination with nab-paclitaxel and gemcitabine. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet one of the discontinuation criteria; whichever occurs first.
nab-paclitaxel + gemcitabine
ACTIVE COMPARATORParticipants will be treated with nab-paclitaxel and gemcitabine. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet one of the discontinuation criteria; whichever occurs first.
Interventions
Administered as an intravenous infusion.
Administered as an intravenous infusion
Administered as an intravenous infusion
Eligibility Criteria
You may qualify if:
- 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.
- +12 more criteria
You may not qualify if:
- 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.
- 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.
- Subjects with positive hepatitis C serology but negative hepatitis C virus RNA test results are eligible.
- 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;
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (136)
St. Joseph Heritage Medical Group
Fullerton, California, 92835, United States
TOI Clinical research
Whittier, California, 90603, United States
Midstate Medical Center
Meriden, Connecticut, 06451, United States
Lynn Cancer Institute
Boca Raton, Florida, 33486, United States
Baptist Health
Miami, Florida, 33176, United States
Cancer Treatment Centers of Atlanta
Newnan, Georgia, 30265, United States
University of Illinois at Chicago
Chicago, Illinois, 60612, United States
Norton Cancer Institute (NCI)
Louisville, Kentucky, 40202, United States
Ochsner Health System
New Orleans, Louisiana, 70121, United States
David C Pratt Cancer Center
Creve Coeur, Missouri, 63141, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Roswell Park Cancer Institute
Buffalo, New York, 14203, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Northwell Health Cancer Institute
Lake Success, New York, 11042, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10022, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204, United States
Novant Health
Winston-Salem, North Carolina, 27103, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
MultiCare Regional Cancer Center - Gig Harbor
Gig Harbor, Washington, 98335, United States
Vista Oncology
Olympia, Washington, 98502, United States
Virginia Mason
Seattle, Washington, 98101, United States
Site AU61008
Gosford, New South Wales, NSW 2250, Australia
Site AU61007
Wollongong, New South Wales, HVGM+3C, Australia
Site AU61005
Fitzroy, Victoria, 5XRF+WX, Australia
Site AU61006
Warrnambool, Victoria, VIC 3280, Australia
Site BR55012
Porto Alegre, Rio Grande do Sul, Brazil
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
Site CN86004
Guangdong, China
Site CN86020
Guangdong, China
Site CN86016
Guangzhou, China
Site CN86012
Harbin, China
Site CN86002
Hubei, China
Site CN86005
Jiangsu, China
Site CN86011
Jiangsu, China
Site CN86025
Jiangsu, China
Site CN86023
Shandong, China
Site CN86006
Shanghai, China
Site CN86013
Shanghai, China
Site CN86019
Shanghai, China
Site CN86007
Tianjin, China
Site CN86022
Xinjiang, China
Site CN86024
Yanxi, China
Site CN86003
Zhejiang, China
Site CN86018
Zhejiang, China
Site CN86010
Zhengzhou, China
Site FR33008
Besançon, Besancon Cedex, 6XG7+42, France
Site FR33010
Brest, Brest Cedex, 9GV7+4G, France
Site FR33015
Caen, Cedex 5, 14076, France
Site FR33006
Chambray, Cedex 9, 37170, France
Site FR33012
Herblain, Herblain Cedex, 44805, France
Site FR33016
La Chaussée-Saint-Victor, Loir-et-Cher, 41260, France
Site FR33009
Nancy, Nancy Cedex, 54000, France
Site FR33017
Rouen, Normandy, 76000, France
Site FR33003
Aquitaine, Pessac, 33604, France
Site FR33013
Villejuif, Villejuif Cedex, 94805, France
Site FR33001
Bayonne, 64109, France
Site FR33018
Bordeaux, France
Site FR33002
Grenoble, France
Site FR33019
La Roche-sur-Yon, France
Site FR33021
Nice, France
Site FR33023
Pierre-Bénite, France
Site FR33014
Plérin, 22190, France
Site FR33005
Pringy, 74374, France
Site FR33007
Strasbourg, 67000, France
Site IR35301
Elm Park, Dublin, D04 T6F4, Ireland
Site IT39006
Rozzano, Milan, 20089, Italy
Site IT39004
Candiolo, Torino, 10060, Italy
Site IT39002
Cremona, 26100, Italy
Site IT39010
Lombardia, Italy
Site IT39003
Milan, 20141, Italy
Site IT39014
Toscana, Italy
Site IT39008
Veneto, Italy
Site JP81007
Nagoya, Aichi-ken, Japan
Site JP81001
Kashiwa, Chiba, Japan
Site JP81005
Sapporo, Hokkaido, Japan
Site JP81006
Yokohama, Kanagawa, Japan
Site JP81003
Kashihara, Nara, Japan
Site JP81011
Bunkyo-ku, Tokyo, Japan
Site JP81012
Chuo-ku, Tokyo, Japan
Site JP81014
Koto-ku, Tokyo, Japan
Site JP81013
Mitaka, Tokyo, Japan
Site JP81002
Shinjuku-ku, Tokyo, Japan
Site JP81015
Ube, Yamaguchi, Japan
Site JP81004
Fukuoka, Japan
Site JP81010
Osaka, Japan
Site JP81009
Wakayama, Japan
Site MX52004
Distrito Federal, Mexico
Site MX52003
San Luis Potosí City, Mexico
Site MX52005
Veracruz, Mexico
Site KR82005
Seongnam-si, Gyeonggi-do, 013620, South Korea
Site KR82008
Suwon, Gyeonggi-do, South Korea
Site KR82010
Daegu, South Korea
Site KR82009
Gyeonggi-do, South Korea
Site KR82001
Seoul, 03080, South Korea
Site KR82003
Seoul, 120-752, South Korea
Site KR82004
Seoul, 138-736, South Korea
Site KR82007
Seoul, 152-703, South Korea
Site KR82002
Seoul, F3QP+76, South Korea
Site KR82006
Seoul, G234+36, South Korea
Site ES34004
Llobregat, Barcelona, 08908, Spain
Site ES34003
Pamplona, Navarre, 31008, Spain
Site ES34010
Barcelona, 08028, Spain
Site ES34013
Barcelona, 08036, Spain
Site ES34007
Barcelona, 08916, Spain
Site ES34018
Barcelona, Spain
Site ES34021
Barcelona, Spain
Site ES34014
Cáceres, 10003, Spain
Site ES34022
Córdoba, Spain
Site ES34005
Lleida, 25198, Spain
Site ES34015
Madrid, 28027, Spain
Site ES34006
Madrid, 28033, Spain
Site ES34009
Madrid, 28034, Spain
Site ES34026
Málaga, Spain
Site ES34017
Santiago de Compostela, Spain
Site TW88608
New Taipei City, Taiwan
Site TW88602
Taichung, 5M5J+36, Taiwan
Site TW88601
Taipei, 4G9C+W3, Taiwan
Site TW88609
Taipei, Taiwan
Site TR90004
Ankara, Turkey (Türkiye)
Site TR90006
Ankara, Turkey (Türkiye)
Site TR90003
Diyarbakır, Turkey (Türkiye)
Site TR90002
Istanbul, Turkey (Türkiye)
Site TR90001
Konya, Turkey (Türkiye)
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Global Development
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
January 23, 2019
First Posted
January 25, 2019
Study Start
March 15, 2019
Primary Completion (Estimated)
August 31, 2026
Study Completion (Estimated)
August 31, 2026
Last Updated
March 12, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.