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

NCT03528629 | Completed

• 2 other identifiers: 8951-CL-0104jRCT2080223901
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Cancer; Gastro-esophageal Junction (GEJ) Cancer

Keywords

zolbetuximab; IMAB362; pharmacokinetics; tolerability; safety; ASP8951; immunogenicity

Outcome Measures

Primary Outcomes (8)

• Dose Limiting Toxicities (DLT) in Safety Part

  Any of the IMAB362 related AEs specified as the DLTs will be assessed during the first 3 weeks.

  Up to Day 22

• Safety and tolerability assessed by incidence of adverse events (AEs) in Safety Part

  An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) guidelines (Version 4.03).

  Up to 16 months

• Number of participants with laboratory test abnormalities in Safety Part

  Number of participants with potentially clinically significant laboratory values will be reported as AEs.

  Up to 14 months

• Number of participants with body weight abnormalities in Safety Part

  Number of participants with potentially clinically significant body weight change will be reported as AEs.

  Up to 14 months

• Number of participants with vital sign abnormalities in Safety Part

  Number of participants with potentially clinically significant vital sign values will be reported as AEs.

  Up to 14 months

• Number of participants with 12-lead electrocardiogram (ECG) abnormalities in Safety Part

  ECGs will be recorded with the participant in the supine position, after the subject has been lying down for approximately 5 minutes. Any clinically significant adverse changes on the ECG will be reported as AEs.

  Up to 14 months

• Safety assessed by Eastern Cooperative Oncology Group (ECOG) performance status in Safety Part

  Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.

  Up to 14 months

• Objective Response Rate (ORR) by local review in Expansion Part

  ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

  Up to 13 months

Secondary Outcomes (26)

• ORR by local review in Safety Part

  Up to 13 months

• ORR by central review in Expansion Part

  Up to 13 months

• Disease Control Rate (DCR) in Safety Part and Expansion Part

  Up to 13 months

• Progression Free Survival (PFS) in Safety Part and Expansion Part

  Up to 13 months

• Overall Survival (OS) in Safety Part and Expansion Part

  Up to 23 months

Study Arms (3)

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

EXPERIMENTAL

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.

Drug: Zolbetuximab

Safety Part Arm B (IMAB362 dose-3)

EXPERIMENTAL

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

Drug: Zolbetuximab

Expansion Part (IMAB362 dose-1/2)

EXPERIMENTAL

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.

Drug: Zolbetuximab

Interventions

Zolbetuximab DRUG

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

Also known as: IMAB362

Expansion Part (IMAB362 dose-1/2); Safety Part Arm A (IMAB362 dose-1/2); Safety Part Arm B (IMAB362 dose-3)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (1)

Site JP00001

Kashiwa, Chiba, Japan

Location

Related Publications (1)

• 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.

  PMID: 38954176 DERIVED

Related Links

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

MeSH Terms

Conditions

Stomach Neoplasms; Neoplasms

Interventions

zolbetuximab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2018
• First Posted: May 18, 2018
• Study Start: June 8, 2018
• Primary Completion: June 9, 2020
• Study Completion: June 9, 2020
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)