Efficacy and Safety of IMAB362 in Combination With the EOX Regimen for CLDN18.2-positive Gastric Cancer

NCT ID: NCT01630083

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-19
• Study Completion Date: 2019-01-31

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.

Conditions

CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction; CLDN18.2-positive Adenocarcinoma of Esophagus; CLDN18.2-positive Gastric Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT

Study Groups

EOX+zolbetuximab 1000 mg/m^2

Participants 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.

Group Type: EXPERIMENTAL

epirubicin

Intervention Type: DRUG

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

Intervention Type: DRUG

Oxaliplatin will be administered at a dose of 130 mg/m\^2 as a 2-hour intravenous infusion on day 1 of each cycle.

capecitabine

Intervention Type: DRUG

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.

zolbetuximab

Intervention Type: DRUG

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.

EOX Treatment

Participants 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.

Group Type: ACTIVE_COMPARATOR

epirubicin

Intervention Type: DRUG

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

Intervention Type: DRUG

Oxaliplatin will be administered at a dose of 130 mg/m\^2 as a 2-hour intravenous infusion on day 1 of each cycle.

capecitabine

Intervention Type: DRUG

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.

EOX+zolbetuximab 800/600 mg/m^2

Participants 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.

Group Type: EXPERIMENTAL

epirubicin

Intervention Type: DRUG

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

Intervention Type: DRUG

Oxaliplatin will be administered at a dose of 130 mg/m\^2 as a 2-hour intravenous infusion on day 1 of each cycle.

capecitabine

Intervention Type: DRUG

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.

zolbetuximab

Intervention Type: DRUG

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.

Interventions

epirubicin

Epirubicin will be administered at a dose of 50 mg/m\^2 as a 15-minute intravenous infusion on day 1 of each cycle.

Intervention Type: DRUG

oxaliplatin

Oxaliplatin will be administered at a dose of 130 mg/m\^2 as a 2-hour intravenous infusion on day 1 of each cycle.

Intervention Type: DRUG

capecitabine

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.

Intervention Type: DRUG

zolbetuximab

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.

Intervention Type: DRUG

Other Intervention Names

IMAB362

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Executive Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

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

Countries

Bulgaria; Czechia; Germany; Latvia; Russia; Ukraine

Related Links

https://www.clinicaltrials.astellas.com/study/GM-IMAB-001-03/

Link to results and other applicable study documents on the Astellas Clinical Trials website

https://www.trialsummaries.com/Study/StudyDetails?id=25768&tenant=MT_AST_9011

Link to plain language summary of the study on the Trial Results Summaries website

Other Identifiers

2011-005285-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8951-CL-0202

Identifier Type: OTHER

Identifier Source: secondary_id

GM-IMAB-001-03

Identifier Type: -

Identifier Source: org_study_id