A Study of Zolbetuximab (IMAB362) in Adults With Gastric Cancer
ILUSTRO
A Phase 2 Study of Zolbetuximab (IMAB362) as Monotherapy and in Combination With Chemotherapy and/or Immunotherapy in Subjects With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and Locoregional Gastric or GEJ Adenocarcinoma Whose Are Claudin (CLDN) 18.2 Positive
4 other identifiers
interventional
143
6 countries
21
Brief Summary
Zolbetuximab is being studied as a treatment for people with cancer in and around the stomach or cancer where the food pipe (esophagus) joins the stomach (gastroesophageal junction cancer). Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. Zolbetuximab is thought to work by attaching to Claudin 18.2 in their tumor. This switches on the body's immune system to attack the tumor. There is an unmet medical need to treat people with advanced cancer in and around the stomach or gastroesophageal junction cancer. This study will provide more information on zolbetuximab given by itself and in combination with other treatments in adults with advanced stomach or gastroesophageal junction cancer. The study is currently ongoing globally. People in this study will either be treated with zolbetuximab by itself, with zolbetuximab and chemotherapy, with zolbetuximab and a medicine called pembrolizumab, or zolbetuximab with chemotherapy and a medicine called nivolumab. This study is ongoing, but enrollment in any of the treatment options has been completed. In addition, at this stage of the study, treatment in some of these treatment options has completed. The main aim of this study is to check how well zolbetuximab controls tumors when given by itself. Adults with cancer in and around the stomach or gastroesophageal junction cancer can take part. Their cancer is locally advanced unresectable or metastatic and has the CLDN18.2 marker in a tumor sample. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. They may have been previously treated with standard therapies. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, have a specific heart condition or infections. There are different treatments in the study. People who take part will receive just 1 of the treatments. Treatment will be given in cycles. The treatment is given through a vein; this is called an infusion. Some people with advanced disease will have 1 infusion in 3 week (21-day) cycles. Some people will have several infusions in 6 week (42-day) cycles. Some people with cancer in and around the stomach or gastroesophageal junction who have surgery for their cancer will have a few infusions in 2-week (14-day) cycles. This will happen before and after they have surgery for their cancer. People may receive chemotherapy for up to 6 months. Some people enrolled to received zolbetuximab and pembrolizumab, may have received pembrolizumab for up to 2 years. People will visit the clinic on certain days during their treatment; there may be extra visits during the first cycle of treatment. The study doctors will check if people had any medical problems from zolbetuximab and the other study treatments. 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 at certain visits with 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. After the clinic visits end some people will have a telephone health check every 3 months. 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
Started Jun 2018
Longer than P75 for phase_2
21 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
March 29, 2018
CompletedFirst Posted
Study publicly available on registry
April 23, 2018
CompletedStudy Start
First participant enrolled
June 29, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2027
October 20, 2025
October 1, 2025
8.1 years
March 29, 2018
October 17, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR) of zolbetuximab as a single agent by central review (Cohort 1)
The ORR is defined as the proportion of participants with complete or partial objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 (assessed by an independent review committee (IRC)).
Up to 3 months
Secondary Outcomes (73)
Pharmacokinetics (PK) of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity (AUCinf) (Cohorts 1A, 2, 3A, 4 and 5)
Up to 16 months
PK of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Extrapolated to Time Infinity Percentage (AUCinf (%extrap)) (Cohorts 1A, 2, 3A, 4 and 5)
Up to 16 months
PK of zolbetuximab: Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast) (Cohorts 1A, 2, 3A, 4 and 5)
Up to 16 months
PK of zolbetuximab: Area Under the Concentration-Time Curve from the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) (Cohorts 1A, 2, 3A, 4 and 5)
Up to 16 months
PK of zolbetuximab: Maximum Concentration (Cmax) (Cohorts 1A, 2, 3A, 4 and 5)
Up to 16 months
- +68 more secondary outcomes
Study Arms (5)
zolbetuximab (Cohort 1A)
EXPERIMENTALParticipants will be treated with zolbetuximab on a 21-day cycle in which zolbetuximab will be administered as a single agent every 3 weeks until disease progression, toxicity requiring cessation, start of another anti-cancer treatment or other treatment discontinuation criteria are met.
mFOLFOX6 plus zolbetuximab (Cohort 2)
EXPERIMENTALParticipants will be treated with zolbetuximab and mFOLFOX6 on a 42-day cycle in which zolbetuximab is administered on days 1 and 22, and mFOLFOX6 is administered on days 1, 15 and 29; however, for the first cycle, zolbetuximab will be administered on day 3 (instead of day 1) to allow for pharmacokinetic collection. Participants will receive up to 12 mFOLFOX6 treatments (4 cycles). Beginning at cycle 5, participants may continue on 5-FU and leucovorin or folinic acid along with zolbetuximab for the remainder of the study per investigator's discretion. mFOLFOX6 treatment includes oxaliplatin: intravenous \[IV\] infusion, leucovorin: IV infusion, fluorouracil bolus: IV bolus, fluorouracil infusion: continuous IV infusion.
Pembrolizumab plus zolbetuximab (Cohort 3A)
EXPERIMENTALParticipants will be treated with zolbetuximab and pembrolizumab on a 21-day cycle. Loading dose of zolbetuximab will be administered at cycle 1, day 1 followed by maintenance dose of zolbetuximab once every 3 weeks (Q3W). Pembrolizumab will be administered to 3 to 6 subjects at a intravenously on day 1 of every 21-day cycle and will be infused 1 hour after the zolbetuximab infusion is completed. Tolerability and safety of zolbetuximab in combination with pembrolizumab will be evaluated during the 3-week dose-limiting toxicity (DLT) assessment period. If this cycle 1 dose is not tolerable, a lower dose of zolbetuximab in combination with pembrolizumab will subsequently be evaluated.
Zolbetuximab in combination with mFOLFOX6 and nivolumab (Cohort 4A/4B)
EXPERIMENTALParticipants will be treated with zolbetuximab and mFOLFOX6, nivolumab on a 42-day cycle. Cohort 4A: Loading dose of zolbetuximab in combination with nivolumab and mFOLFOX6 on cycle 1 day 1, followed by zolbetuximab in combination with nivolumab and mFOLFOX6 q2w \[days 15 and 29\] (1 cycle = 6 weeks). Tolerability and safety of zolbetuximab in combination with nivolumab, mFOLFOX6 will be evaluated during the 3-week DLT assessment period. If cycle 1 dose is not tolerable, a lower dose of dose zolbetuximab in combination with nivolumab and mFOLFOX6 will be subsequently evaluated. Cohort 4B: Subjects will be treated with the combination of zolbetuximab, mFOLFOX6 and nivolumab at the dose deemed tolerable in Cohort 4A. Subjects will receive up to 12 mFOLFOX6 treatments (4 cycles). For Cohorts 4A and 4B, beginning at cycle 5, subjects may continue on 5-FU and leucovorin or folinic acid along with zolbetuximab and nivolumab for the remainder of the study per investigator's discretion.
Zolbetuximab in combination with FLOT (Cohort 5)
EXPERIMENTALParticipants will be treated with zolbetuximab \& FLOT for a total of eight 2-week cycles. 4 cycles preoperatively \& 4 cycles postoperatively 6-12 weeks after surgery. Preoperative: Participants will receive zolbetuximab loading dose on cycle 1 day 1, followed by FLOT on cycle 1 day 2. For cycles 2-4, participants may receive zolbetuximab maintenance dose in combination with FLOT, dosed on day 1 of each cycle. However, dosing may be split over 2 days with zolbetuximab administration on day 1 \& FLOT on day 2. Post operative: Participants will receive zolbetuximab loading dose on cycle 5 day 1, followed by FLOT on cycle 5 day 2. For cycles 6-8, participants may receive zolbetuximab maintenance dose in combination with FLOT, dosed on day 1 of each cycle. However, dosing may be split over 2 days with zolbetuximab administration on day 1 and FLOT on day 2. For participants who experience a DLT during preoperative treatment on the loading dose, the postoperative loading dose may be lowered.
Interventions
Zolbetuximab will be administered as a minimum 2-hour IV infusion.
Oxaliplatin will be administered as a 2-hour IV infusion.
Leucovorin will be administered as a 2-hour IV infusion.
Fluorouracil will be administered as IV bolus over 5 to 15 minutes and continuous IV infusion over 46 to 48 hours or per institutional guidelines.
Pembrolizumab will be administered intravenously over 30 minutes.
Folnic acid will be administered as a 2-hour IV infusion.
Nivolumab will be administered intravenously according to institutional standards.
Docetaxel will be administered as a 1-hour IV infusion.
Eligibility Criteria
You may qualify if:
- Female subject eligible to participate if she is not pregnant and at least one of the following conditions applies:
- Not a woman of child-bearing potential (WOCBP) OR
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs.
- 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 agree not to donate ova starting at screening and throughout the study period, and for 9 months after the final oxaliplatin administration and 6 months after the final administration of all other study drugs.
- A sexually active male subject with a female partner(s) who is 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.
- Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 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 has histologically confirmed gastric or GEJ adenocarcinoma.
- Cohorts 1-4: Subject has radiographically-confirmed, locally advanced, unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
- Subject's tumor is positive for CLDN18.2 expression demonstrating moderate to strong membranous staining as determined by central IHC testing.
- Subject agrees to not participate in another interventional study while on treatment.
- Subject has ECOG performance status 0 to 1.
- Subject has predicted life expectancy ≥ 12 weeks.
- Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to the first dose of study treatment. In case of multiple central laboratory data within this period, the most recent data should be used.
- +39 more criteria
You may not qualify if:
- Subject has had prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
- Subject has known immediate or delayed hypersensitivity or contraindication to any component of study treatment.
- Subject has received other investigational agents or devices concurrently or within 28 days prior to first dose of study treatment.
- Subject has received systemic immunosuppressive therapy, including systemic corticosteroids 14 days prior to first dose of study treatment.
- Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent recurrent vomiting.
- Subject has significant gastric bleeding and/or untreated gastric ulcers that would preclude the subject from participation.
- Subject has history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.
- Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen \[HBsAg\]) or hepatitis C infection.
- Subject has had within 6 months prior to first dose of study treatment any of the following: unstable angina, myocardial infarction, ventricular arrhythmia requiring intervention or hospitalization for heart failure.
- Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to the start of study treatment.
- Subject has active autoimmune disease that has required systemic treatment within the past 3 months prior to the start of study treatment.
- Subject has a clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this study or make the subject unsuitable for study participation.
- Subject has psychiatric illness or social situations that would preclude study compliance.
- Subject has had a major surgical procedure ≤ 28 days before start of study treatment.
- Subject is without complete recovery from a major surgical procedure ≤ 14 days before start of study treatment
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
The Angeles Clinic and Research Institute
Los Angeles, California, 90025, United States
UCLA Medical Center
Santa Monica, California, 90404, United States
University of Chicago
Chicago, Illinois, 60637, United States
Mass General / North Shore Can
Boston, Massachusetts, 02114, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Weill Cornell Medical College
New York, New York, 10065, United States
Site FR33003
Pessac, Nouvelle-Aquitaine, 33604, France
Site FR33002
Poitiers, Nouvelle-Aquitaine, 86021, France
Site FR33001
Brest, France
Site FR33004
Paris, 75015, France
Site IT39005
Milan, Italy
Site IT39002
Napoli, Italy
Site IT39004
Padua, Italy
Site IT39003
Pisa, Italy
Site JP81001
Chiba, Japan
Site JP81002
Tokyo, Japan
Site JP81003
Tokyo, Japan
Site KR82002
Seongnam-si, South Korea
Site KR82001
Seoul, South Korea
Site TW88601
Taichung, Taiwan
Site TW88602
Tainan, 70403, Taiwan
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Global Medical Lead
Astellas Pharma Global Development, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- Participants will be enrolled to receive zolbetuximab as monotherapy or in combination with mFOLFOX6 (with or without Nivolumab) and in combination with pembrolizumab and in combination with FLOT in an unblinded fashion.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
March 29, 2018
First Posted
April 23, 2018
Study Start
June 29, 2018
Primary Completion (Estimated)
July 31, 2026
Study Completion (Estimated)
May 31, 2027
Last Updated
October 20, 2025
Record last verified: 2025-10
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/.