Clinical trial NCT04086758: A Pharmacokinetic Study of Zolbetuximab (IMAB362) in Chinese Subjects With Locally Advanced Unresectable or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma
Official title: A Phase 1 Pharmacokinetic Study of Zolbetuximab (IMAB362) in Chinese Subjects With Locally Advanced Unresectable or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma
Keywords: Pharmacokinetic
MDV3100
zolbetuximab
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2019-09-12
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Pharmacokinetic Study of Zolbetuximab (IMAB362) in Chinese Subjects with Locally Advanced Unresectable or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma


Eligibility criteria: Inclusion Criteria:

* Subject has histologically confirmed diagnosis of gastric or gastro-esophageal junction (GEJ) adenocarcinoma, with radiologically confirmed locally advanced unresectable or metastatic disease, who has no standard of care treatment option or subject is ineligible to receive available standard of care treatment option (any line of treatment).
* Subject agrees not to use another investigational product or medical device while on treatment.
* A female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin (βhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies:

  * Not a woman of childbearing potential (WOCBP), OR
  * WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration.
* Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 6 months after the final study drug administration.
* Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
* A sexually active male subject with female partner(s) who are not of childbearing potential is eligible if:

  * Agree to use a male condom starting at screening and continue throughout study treatment and for 6 months after the final study drug administration.
* A sexually active male subject with female partner(s) who are of childbearing potential must agree to use contraception during the treatment and for at least 6-months after the final study drug administration.
* Male subject must not donate sperm starting at Screening, throughout the study period and for 6 months after the final study drug administration.
* Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding from the start of screening to 6 months after the final study drug administration.
* 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 following criteria on the laboratory tests that will be analyzed locally within 14 days prior to the first dose of study drug. In case of multiple laboratory data within this period, the most recent data should be used.

  * Hemoglobin (Hgb) ≥ 9 g/dL (no transfusion within 7 days of start of study treatment)
  * Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L
  * Platelets ≥ 100 × 10\^9/L
  * Albumin ≥ 2.5 g/dL
  * Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN without liver metastases (≤ 5 x ULN if liver metastases are present)
  * Estimated creatinine clearance ≥ 30 mL/min
  * Prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 × ULN (except for patients receiving anticoagulation therapy)
* Subject's tumor sample has Claudin (CLDN) 18.2 membranous staining in tumor cells with any intensity (≥ 1) as determined by central Immunohistochemistry (IHC) testing.

Exclusion Criteria:

* Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies like zolbetuximab.
* Subject has received another investigational product or medical device concurrently or within 4 weeks prior first dose of study drug.
* Subject has had radiotherapy within 2 weeks prior to first dose of study treatment. Subject who received palliative radiotherapy to peripheral bone metastases within 2 weeks prior to first dose of study treatment and has recovered from all acute toxicities is allowed.
* 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 (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) or a single dose of systemic corticosteroid are allowed.
* Subject has gastric outlet obstruction 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, an HB 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 ≤ 28 days prior to the first dose of study drug.

  * Subject has not completely recovered from a major surgical procedure ≤ 14 days prior to the first dose of study treatment.
* 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: Pharmacokinetics (PK) of zolbetuximab: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Percentage of AUCinf (AUCinf (%extrap))
timeFrame: Up to 15 months
measure: PK of zolbetuximab: AUC from the time of dosing to the last measurable concentration (AUClast)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: AUC from the time of dosing to the start of the next dosing interval (AUCtau)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Maximum concertation (Cmax)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Concentration immediately prior to dosing at multiple dosing (Ctrough)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Time of the maximum concentration (tmax)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Terminal elimination half-life (t1/2)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Time of the last measurable concentration (tlast)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Clearance (CL)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Apparent volume of distribution during the terminal phase (Vz)
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Accumulation ratio calculated using AUC (Rac(AUC))
timeFrame: Up to 15 months
measure: PK of zolbetuximab: Rac (Cmax)
timeFrame: Up to 15 months
measure: Number of participants with adverse events (AEs)
timeFrame: Up to 15 months
measure: Number of participants with laboratory test abnormalities and/or AEs
timeFrame: Up to 13 months
measure: Number of participants with body weight abnormalities and/or AEs
timeFrame: Up to 13 months
measure: Number of participants with vital sign abnormalities and/or AEs
timeFrame: Up to 13 months
measure: Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs
timeFrame: Up to 13 months
measure: Eastern Cooperative Oncology Group (ECOG) performance status score
timeFrame: Up to 13 months
Secondary outcomes:
measure: Proportion of anti-drug antibody (ADA) positive participants
timeFrame: Up to 15 months
measure: Objective Response Rate (ORR)
timeFrame: Up to 12 months
measure: Duration of Progression Free Survival (PFS)
timeFrame: Up to 12 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 12 months
measure: Duration of Response (DOR)
timeFrame: Up to 12 months
measure: Duration of Overall Survival (OS)
timeFrame: Up to 15 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Site CN86001
Study officials:
affiliation: Astellas Pharma China, Inc.
name: Medical Science Manager
role: STUDY_DIRECTOR
References: