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

CLDN18.2-positive Adenocarcinoma of Esophagus Clinical Trial

— FAST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01630083
• Other study ID #: GM-IMAB-001-03
• Secondary ID: 2011-005285-3889
• Status: Completed
• Phase: Phase 2
• Start date: July 19, 2012
• Est. completion date: January 31, 2019

Study information

• Verified date: January 2020
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: January 31, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Bulgaria	Site BUL004	Plovdiv
Bulgaria	Site BUL001	Sofia
Bulgaria	Site BUL003	Sofia
Bulgaria	Site BUL005	Sofia
Bulgaria	Site BUL002	Varna
Czechia	Site CZE002	Olomouc
Czechia	Site CZE001	Znojmo
Germany	Site GER012	Bielefeld
Germany	Site GER029	Bochum
Germany	Site GER029-01	Bochum
Germany	Site GER010	Dresden
Germany	Site GER001	Essen
Germany	Site GER017	Frankfurt
Germany	Site GER005	Halle/Saale
Germany	Site GER020	Leipzig
Germany	Site GER016	Münster
Germany	Site GER013	Pinneberg
Latvia	Site LAT001	Liepaja
Latvia	Site LAT002	Riga
Russian Federation	Site RUS011	Arkhangelsk
Russian Federation	Site RUS016	Bryansk
Russian Federation	Site RUS006	Chelyabinsk
Russian Federation	Site RUS007	Ivanovo
Russian Federation	Site RUS009	Kursk
Russian Federation	Site RUS001	Moscow
Russian Federation	Site RUS017	Novgorod
Russian Federation	Site RUS002	Obninsk
Russian Federation	Site RUS023	Omsk
Russian Federation	Site RUS012	Orel
Russian Federation	Site RUS014	Orenburg
Russian Federation	Site RUS005	Pyatigorsk
Russian Federation	Site RUS019	Ryazan
Russian Federation	Site RUS003	St.Petersburg
Russian Federation	Site RUS010	St.Petersburg
Russian Federation	Site RUS015	St.Petersburg
Russian Federation	Site RUS013	Yaroslavl
Ukraine	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

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Germany,  Latvia,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	Clinical PFS	Clinical PFS (CPFS) is defined as the time from randomization to the first observation of disease progression, either confirmed by computed tomography (CT) scans or by clinical evaluation, or death from any cause (as assessed by the independent reviewer with clinical PD considered as an event). 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.
Secondary	Overall Survival Rate at 12 Months	Overall survival rate at 12 months after therapy initiation is defined as a proportion of participants alive after 12 months from first dose of any study drug.	Up to 12 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death from any cause or last contact (if alive).	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.
Secondary	Time to Progression (TTP)	TTP is defined as the time from randomization to the first observation of disease progression (based on central reading as assessed by the investigator reviewer). Participants without documented progression 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.
Secondary	Objective Tumor Response Rate (ORR)	ORR is defined as the fraction of participants with a complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (as assessed by the investigator reviewer). CR according to RECIST v1.1 is defined as the disappearance of all target lesions, any pathological lymph node must have reduction in short axis to < 10 mm, disappearance of all non-target lesions and normalization of tumor marker level should occur as well as no simultaneous appearance of new lesions. PR according to RECIST v1.1 is defined as at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter and no simultaneous increase in the size of any lesion or the appearance of new lesions.	Up to week 94
Secondary	Disease Control Rate (DCR)	DCR is defined as the fraction of participants with CR or PR or stable disease (SD) according to RECIST v1.1 (as assessed by the investigator reviewer). SD according to RECIST v1.1 is defined as neither sufficient shrinkage to qualify for PR or CR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter recorded since treatment started, measurements must meet the SD criteria at least once after study entry at a minimum interval not less than 6 weeks, no simultaneous increase in the size of any lesion or the appearance of new lesions should occur, evaluable lesions must remain stable or regress for this category.	Up to week 94
Secondary	Duration of Response (DOR)	DOR will be determined as the time when criteria for CR or PR are first met until the first date that recurrent or progressive disease or death occurs (as assessed by the independent reviewer).	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.