A Study of IMAB362 in Japanese Subjects With Locally Advanced or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma

NCT ID: NCT03528629

Last Updated: 2024-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-08

Study Completion Date

2020-06-09

Brief Summary

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The purpose of this study is to assess the safety, tolerability and antitumor activity of IMAB362 in Japanese subjects with locally advanced or metastatic Gastric or GEJ adenocarcinoma whose tumors have Claudin (CLDN) 18.2 Expression. This study will also assess pharmacokinetics and immunogenicity of IMAB362.

Detailed Description

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This study consists of two parts (Part 1: Safety; and Part 2: Expansion). First, the subjects will be enrolled in Safety Part with IMAB362 dose-1/2 (Arm A). Then the safety and tolerability of Arm A will be evaluated at Tolerability Evaluation Meeting (TEM). If there are no safety and tolerability concerns, enrollment for the Safety Part with IMAB362 dose-3 (Arm B) and the Expansion Part with IMAB362 dose-1/2 will be opened. For each part, participants who continue to derive clinical benefit and do not have intolerable toxicity from study treatment will be allowed to remain on treatment until treatment discontinuation criterion is met.

Conditions

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Gastric Cancer Gastro-esophageal Junction (GEJ) Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Safety Part Arm A (IMAB362 dose-1/2)

Participants will receive a loading dose-1 of IMAB362 on Cycle 1 Day 1 followed by a lower dose-2 in subsequent every 3 weeks.

Group Type EXPERIMENTAL

Zolbetuximab

Intervention Type DRUG

Zolbetuximab will be administered as a 2-hour intravenous infusion.

Safety Part Arm B (IMAB362 dose-3)

Participants will receive a loading dose-3 of IMAB362 on Day 1 of each cycle (every 3 weeks).

Group Type EXPERIMENTAL

Zolbetuximab

Intervention Type DRUG

Zolbetuximab will be administered as a 2-hour intravenous infusion.

Expansion Part (IMAB362 dose-1/2)

Participants will receive a loading dose-1 of IMAB362 on Cycle 1 Day 1 followed by a lower dose-2 in subsequent every 3 weeks.

Group Type EXPERIMENTAL

Zolbetuximab

Intervention Type DRUG

Zolbetuximab will be administered as a 2-hour intravenous infusion.

Interventions

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Zolbetuximab

Zolbetuximab will be administered as a 2-hour intravenous infusion.

Intervention Type DRUG

Other Intervention Names

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IMAB362

Eligibility Criteria

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Inclusion Criteria

* Subject has histologically or cytologically confirmed diagnosis of gastric or gastro-esophageal junction adenocarcinoma.
* Subject has gastric or gastroesophageal junction (GEJ) adenocarcinoma based on radiographic imaging or endoscopic examination.
* Subject agrees not to participate in another interventional study while on treatment.
* Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Subject has predicted life expectancy ≥ 12 weeks.
* Subject must have an available tumor specimen collected at any time prior to the first dose of study treatment.
* Subject must meet all of the pre-specified criteria on the laboratory tests that will be analyzed locally within 7 days prior to the first dose of study drug.
* Locally advanced or Metastatic gastric or GEJ adenocarcinoma with no standard of care treatment option or subject is ineligible to receive available standard of care treatment option.
* Subject's tumor sample has Claudin (CLDN)18.2 membranous staining with any intensity as determined by central Immunohistochemistry (IHC) testing. (Safety part only)
* Subject has CLDN18.2 high expression in ≥75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing. (Expansion Part Only)
* Subject is an appropriate candidate for a tumor biopsy and is amenable to undergo a tumor biopsy during the Screening period and on-treatment tumor biopsy. (Expansion Part Only)
* Subject has at least 1 measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 within 28 days prior to the first dose of study treatment. 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. (Expansion Part Only)

Exclusion Criteria

* Subject has prior severe allergic reaction or intolerance to a monoclonal antibody, including humanized or chimeric antibodies.
* Subject has had radiotherapy within 2 weeks prior to first dose of study drug. Subject who received palliative radiotherapy to peripheral bone metastases within 2 weeks prior to first dose of study drug and has recovered from all acute toxicities is allowed.
* Subject has received other investigational agents or devices concurrently or within 4 weeks prior first dose of study drug.
* Subject has received systemic immunosuppressive therapy, including systemic corticosteroids 2 weeks prior to first dose of study drug. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent are allowed.
* Subject has gastric outlet syndrome or persistent recurrent vomiting.
* Subject has uncontrolled or significant gastrointestinal hemorrhage.
* Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection.
* Subject has a positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (anti-HCV). Subjects who are negative for HBsAg, but hepatitis B core antibody (HBcAb) positive, hepatitis B virus deoxyribonucleic acid (DNA) test will be performed and if positive will be excluded. Subjects with positive serology but negative HCV ribonucleic acid (RNA) test results are eligible.
* 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.
* Subject has clinically significant other disease or co-morbidity, which may adversely affect the safe delivery of treatment within this trial.
* Subject has psychiatric illness or social situations that would preclude study compliance.
* Subject has active autoimmune disease that has required systemic immunosuppressive treatment in the past 2 years.
* Subject has had a major surgical procedure within 28 days prior to the first dose of study drug.
* Subject has Fridericia-corrected QT interval (QTcF) \> 450 msec for males and \> 470 msec for females on 12-lead electrocardiogram (ECG) at screening based on local testing.
* Subject has any condition which makes the subject unsuitable for study participation.
* Subject has another active malignancy which is likely to require treatment.
* Subjects who find it difficult to adhere to the provisions of treatment and observation specified in the protocol.
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Astellas Pharma Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Inc

Locations

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Site JP00001

Kashiwa, Chiba, Japan

Site Status

Countries

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Japan

References

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Shitara K, Xu RH, Ajani JA, Moran D, Guerrero A, Li R, Pavese J, Matsangou M, Bhattacharya P, Ueno Y, Wang X, Shah MA. Global prevalence of claudin 18 isoform 2 in tumors of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Gastric Cancer. 2024 Sep;27(5):1058-1068. doi: 10.1007/s10120-024-01518-1. Epub 2024 Jul 2.

Reference Type DERIVED
PMID: 38954176 (View on PubMed)

Related Links

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http://www.trialsummaries.com/Study/StudyDetails?id=25727&tenant=MT_AST_9011

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

Other Identifiers

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jRCT2080223901

Identifier Type: OTHER

Identifier Source: secondary_id

8951-CL-0104

Identifier Type: -

Identifier Source: org_study_id