Efficacy and Safety of IMAB362 in Combination With the EOX Regimen for CLDN18.2-positive Gastric Cancer
FAST
A Randomized Phase II Multicenter, Open-Label Study Evaluating the Efficacy and Safety of IMAB362 in Combination With the EOX (Epirubicin, Oxaliplatin, Capecitabine) Regimen as First-Line Treatment of Patients With CLDN18.2-Positive Advanced Adenocarcinomas of the Stomach, the Esophagus or the Gastroesophageal Junction
3 other identifiers
interventional
252
6 countries
48
Brief Summary
The purpose of the trial is to assess the therapeutic effects and the safety profile of IMAB362 combined with EOX (epirubicin, oxaliplatin, capecitabine) as first-line treatment for patients with advanced adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction compared to EOX alone. Furthermore, sufficient binding of IMAB362 to the target cells is necessary for antitumoral activity. Thus, two dose levels ensuring a serum level above the in vitro predicted clinical efficacy threshold will be investigated.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2012
Longer than P75 for phase_2
48 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 19, 2012
CompletedFirst Posted
Study publicly available on registry
June 28, 2012
CompletedStudy Start
First participant enrolled
July 19, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2019
CompletedJune 15, 2025
June 1, 2025
6.5 years
June 19, 2012
June 12, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-free survival (PFS)
PFS is defined as the time from randomization to the first observation of disease progression (based on central reading) or death from any cause (as assessed by the independent reviewer). Participants without documented progression or death will be censored as of the last tumor evaluation determining lack of progression.
From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
Number of Participants with Adverse Events (AEs)
An AE is defined as any unintended or undesirable, noxious or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study medication. Treatment-emergent adverse event (TEAE) are those AEs that started or worsened after the first dose of study medication.
From the first dose of study drug administration up to 30 days after the last study medication administration (up to 1791 days).
Secondary Outcomes (7)
Clinical PFS
From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
Overall Survival Rate at 12 Months
Up to 12 months
Overall Survival (OS)
From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
Time to Progression (TTP)
From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
Objective Tumor Response Rate (ORR)
Up to week 94
- +2 more secondary outcomes
Study Arms (3)
EOX Treatment
ACTIVE COMPARATORParticipants will receive up to 8 cycles of epirubicin, oxaliplatin and capecitabine (EOX) chemotherapy treatment alone (50 mg/m\^2 epirubicin intravenously on day 1 of each cycle, 130 mg/m\^2 oxaliplatin intravenously on day 1 of each cycle, 625 mg/m\^2 capecitabine orally twice daily on days 1 to 21 of each cycle). The first dose of capecitabine to be taken in the evening of day 1.
EOX+zolbetuximab 800/600 mg/m^2
EXPERIMENTALParticipants will received up to 8 cycles of EOX chemotherapy treatment in combination with zolbetuximab administered as loading dose of 800 mg/m\^2 intravenously on day 1 of cycle 1 followed by 600 mg/m\^2 intravenously on day 1 of each subsequent cycle. Zolbetuximab to be administered prior to EOX chemotherapy. After completion of the EOX treatment phase, participants will be permitted to continue zolbetuximab monotherapy (600 mg/m\^2 every 3 weeks to be administered intravenously as a 2-hour infusion) until progressive disease (PD), withdrawal of consent or unacceptable toxicity. PD per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study, an absolute increase of at least 5mm must also be demonstrated, unequivocal progression of existing non-target lesions and appearance of one or more new lesions is considered progression.
EOX+zolbetuximab 1000 mg/m^2
EXPERIMENTALParticipants will receive up to 8 cycles of EOX chemotherapy treatment in combination with zolbetuximab 1000 mg/m\^2 intravenously on day 1 of each cycle. Zolbetuximab to be administered prior to EOX chemotherapy. After completion of the EOX treatment phase, participants will be permitted to continue zolbetuximab monotherapy (1000 mg/m\^2 every 3 weeks administered intravenously as a 2-hour infusion ) until PD, withdrawal of consent or unacceptable toxicity.
Interventions
Epirubicin will be administered at a dose of 50 mg/m\^2 as a 15-minute intravenous infusion on day 1 of each cycle.
Oxaliplatin will be administered at a dose of 130 mg/m\^2 as a 2-hour intravenous infusion on day 1 of each cycle.
The daily dose of capecitabine will be 1250 mg/m\^2. Capecitabine tablets to be given once daily at a dose of 625 mg/m\^2 orally in the evening of day 1 of each cycle and twice daily at a dose of 625 mg/m\^2 orally on days 2 to 21 of each cycle; the morning dose of capecitabine on day 1 of each cycle to be omitted due to administration of zolbetuximab, epirubicin and oxaliplatin.
Two different formats of zolbetuximab, comprising different strengths, to be provided. Vials contained 22 mg or 105 mg of zolbetuximab. Prior to administration, zolbetuximab will be reconstituted with 1.1 mL (22 mg zolbetuximab vials) or 5.0 mL (105 mg zolbetuximab vials) water for injection, which will result in a concentration of 20 mg/mL zolbetuximab. The extractable volume per vial will be 1 mL (for 22 mg zolbetuximab vials) or 5 mL (for 105 mg zolbetuximab vials). The reconstituted solution will be further diluted with sodium chloride 0.9% to a final concentration of 2 mg/mL zolbetuximab. Zolbetuximab will be administered as an intravenous infusion over 2 to 3 hours.
Eligibility Criteria
You may qualify if:
- Histologically confirmed adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction
- Inoperable locally advanced disease or resections with R2 outcome or recurrent or metastatic disease.
- CLDN18.2 expression confirmed by immunohistochemistry in paraffin embedded tumor tissue sample.
- Measurable and/or non-measurable disease as defined according to RECISTv1.1
- Age ≥ 18 years
- Written Informed Consent Form
- ECOG performance status (PS) 0-1
- Life expectancy \> 3 months
- HER2/neu negative patients and patients with HER2/neu positive status but not eligible to trastuzumab therapy in discretion of the investigator.
- Adequate cardiac, hepatic, renal, hematologic function.
You may not qualify if:
- Prior severe allergic reaction or intolerance to a monoclonal antibody, to the chemotherapeutics used in this study or any excipient in the respective formulations.
- Previous chemotherapy for advanced disease.
- Previous perioperative chemotherapy with curative intention within 6 months of start of study treatment. If interval is longer than 6 months (counted from the stop date of the perioperative chemotherapy), patients are allowed.
- Known HIV infection or known symptomatic hepatitis (A, B, C).
- Symptomatic cerebral metastases.
- Pregnancy or breastfeeding.
- Previous treatments with maximum cumulative doses of epirubicin \> 500 mg/m² and/or other anthracyclines and anthracenediones.
- Known dihydropyrimidine dehydrogenase (DPD) deficiency.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (48)
Site BUL004
Plovdiv, Bulgaria
Site BUL001
Sofia, Bulgaria
Site BUL003
Sofia, Bulgaria
Site BUL005
Sofia, Bulgaria
Site BUL002
Varna, Bulgaria
Site CZE002
Olomouc, Czechia
Site CZE001
Znojmo, Czechia
Site GER012
Bielefeld, Germany
Site GER029-01
Bochum, Germany
Site GER029
Bochum, Germany
Site GER010
Dresden, Germany
Site GER001
Essen, Germany
Site GER017
Frankfurt, Germany
Site GER005
Halle, Germany
Site GER020
Leipzig, Germany
Site GER016
Münster, Germany
Site GER013
Pinneberg, Germany
Site LAT001
Liepāja, Latvia
Site LAT002
Riga, Latvia
Site RUS011
Arkhangelsk, Russia
Site RUS016
Bryansk, Russia
Site RUS006
Chelyabinsk, Russia
Site RUS007
Ivanovo, Russia
Site RUS009
Kursk, Russia
Site RUS001
Moscow, Russia
Site RUS002
Obninsk, Russia
Site RUS023
Omsk, Russia
Site RUS014
Orenburg, Russia
Site RUS012
Oryol, Russia
Site RUS005
Pyatigorsk, Russia
Site RUS019
Ryazan, Russia
Site RUS003
Saint Petersburg, Russia
Site RUS010
Saint Petersburg, Russia
Site RUS015
Saint Petersburg, Russia
Site RUS017
Veliky Novgorod, Russia
Site RUS013
Yaroslavl, Russia
Site UKR003
Dnipropetrovsk, Ukraine
Site UKR001
Donetsk, Ukraine
Site UKR002
Donetsk, Ukraine
Site UKR008
Ivano-Frankivsk, Ukraine
Site UKR005
Kharkiv, Ukraine
Site UKR007
Kyiv, Ukraine
Site UKR006
Lviv, Ukraine
Site UKR015
Poltava, Ukraine
Site UKR004
Simferopol, Ukraine
Site UKR011
Sumy, Ukraine
Site UKR010
Uzhhorod, Ukraine
Site UKR009
Zaporizhia, Ukraine
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Executive Director
Astellas Pharma Global Development, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 19, 2012
First Posted
June 28, 2012
Study Start
July 19, 2012
Primary Completion
January 31, 2019
Study Completion
January 31, 2019
Last Updated
June 15, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will not share
Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.