Clinical trial NCT03528629: A Study of IMAB362 in Japanese Subjects With Locally Advanced or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma
Official title: A Phase 1 Open-label Study of IMAB362 in Japanese Subjects With Locally Advanced or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastric Cancer
Gastro-esophageal Junction (GEJ) Cancer
Keywords: zolbetuximab
IMAB362
pharmacokinetics
tolerability
safety
ASP8951
immunogenicity
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2018-05-18
Enrollment: 18
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLT) in Safety Part
timeFrame: Up to Day 22
measure: Safety and tolerability assessed by incidence of adverse events (AEs) in Safety Part
timeFrame: Up to 16 months
measure: Number of participants with laboratory test abnormalities in Safety Part
timeFrame: Up to 14 months
measure: Number of participants with body weight abnormalities in Safety Part
timeFrame: Up to 14 months
measure: Number of participants with vital sign abnormalities in Safety Part
timeFrame: Up to 14 months
measure: Number of participants with 12-lead electrocardiogram (ECG) abnormalities in Safety Part
timeFrame: Up to 14 months
measure: Safety assessed by Eastern Cooperative Oncology Group (ECOG) performance status in Safety Part
timeFrame: Up to 14 months
measure: Objective Response Rate (ORR) by local review in Expansion Part
timeFrame: Up to 13 months
Secondary outcomes:
measure: ORR by local review in Safety Part
timeFrame: Up to 13 months
measure: ORR by central review in Expansion Part
timeFrame: Up to 13 months
measure: Disease Control Rate (DCR) in Safety Part and Expansion Part
timeFrame: Up to 13 months
measure: Progression Free Survival (PFS) in Safety Part and Expansion Part
timeFrame: Up to 13 months
measure: Overall Survival (OS) in Safety Part and Expansion Part
timeFrame: Up to 23 months
measure: Duration of Response (DOR) in Safety Part and Expansion Part
timeFrame: Up to 13 months
measure: Pharmacokinetics (PK) of IMAB362 in Safety Part and Expansion Part: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Percentage of AUCinf (AUCinf (%extrap))
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: AUC from the time of dosing to the last measurable concentration (AUClast)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: AUC from the time of dosing to the start of the next dosing interval (AUCtau)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Maximum concentration (Cmax)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Concentration immediately prior to dosing at multiple dosing (Ctrough)
timeFrame: Up to 16 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Time of the maximum concentration (tmax)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Terminal elimination half-life (t1/2)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Clearance (CL)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Apparent volume of distribution at steady state (Vss)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Apparent volume of distribution during the terminal phase (Vz)
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Accumulation ratio calculated using AUC (Rac(AUC))
timeFrame: Up to 3 months
measure: PK of IMAB362 in Safety Part and Expansion Part: Rac (Cmax)
timeFrame: Up to 3 months
measure: Safety assessed by incidence of AEs in Expansion Part
timeFrame: Up to 16 months
measure: Number of participants with laboratory test abnormalities in Expansion Part
timeFrame: Up to 14 months
measure: Number of participants with vital sign abnormalities in Expansion Part
timeFrame: Up to 14 months
measure: Number of participants with body weight abnormalities in Expansion Part
timeFrame: Up to 14 months
measure: Number of participants with 12-lead ECG abnormalities in Expansion Part
timeFrame: Up to 14 months
measure: Safety assessed by ECOG performance status in Expansion Part
timeFrame: Up to 14 months
measure: Frequency of anti-drug antibody (ADA)-positive participants in Safety Part and Expansion Part
timeFrame: Up to 16 months
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: Site JP00001
state: Chiba
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: