Safety and Tolerability Study of Claudiximab in Patients With Advanced Gastroesophageal Cancer

Clinical First-in-human Single-dose Escalation Study Evaluating the Safety and Tolerability of Claudiximab (iMAB-362) in Hospitalized Patients With Advanced Gastroesophageal Cancer. A Multi-center, Phase I, Open-label, i.v. Infusion Study

Claudiximab is a monoclonal antibody specific for gastric and gastroesophageal adenocarcinomas. Preclinically, claudiximab was shown to inhibit tumor growth and to kill cancer cells by indirect (complement-dependent cytoxicity, antibody-dependent cellular cytotoxicity) and direct mechanisms (antiproliferative and proapoptotic effects). The aim of this phase I study is to establish safety, toxicity and maximal tolerable dose of a single infusion of claudiximab in patients suffering from relapsing, advanced gastroesophageal and gastric adenocarcinoma

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Claudiximab

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45122
    • Universitätsklinikum Essen, Innere Klinik (Tumorforschung)
  • Heidelberg, Germany, 69120
    • Universität Heidelberg, Nationales Centrum für Tumorerkrankungen (NCT)
  • Mainz, Germany, 55131
    • Johannes Gutenberg Universität, 1.Med Klinik und Poliklinik
  • München, Germany, 81674
    • Klinikum Rechts-der-Isar, III.Medizinische Klinik und Poliklinik
• Latvia
  • Liepaja, Latvia, 3401
    • Piejuras Hospital
  • Riga, Latvia, 1002
    • Pauls Stradins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Metastatic, refractory or recurrent disease of advanced gastroesophageal cancer (adenocarcinoma) proven by histology
• CLDN18.2 expression confirmed by immunohistochemistry
• Prior standard chemotherapy containing a fluoropyrimidine, a platinum compound and/or epirubicine, and - if clinically appropriate - docetaxel
• At least 1 measurable site of the disease according RECIST criteria (CT-scans or MRT not older than 6 weeks before study entry)
• Age ≥ 18 years
• ECOG performance status (PS) 0-1 or Karnofsky Index 70-100%
• Life expectancy > 3 months
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 g/dl
• INR < 1.5
• Bilirubin normal
• AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Creatinine < 1.5 x ULN

Exclusion Criteria:

• Pregnancy or breastfeeding
• Prior allergic reaction or intolerance to a monoclonal antibody
• Prior inclusion in the present study
• Less than 3 weeks since prior anti-tumor or radiation therapy
• Other investigational agents or devices concurrently or within 4 weeks prior to this study
• Other concurrent anticancer therapies
• History of positive test for human immunodeficiency virus (HIV) antibody
• Known Hepatitis.
• Uncontrolled or severe illness.
• Concurrent administration of anticoagulation agents with vitamin K antagonists
• Concurrent administration of therapeutic doses of heparin (prophylactic doses are acceptable)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Claudiximab

Drug: Claudiximab; Patients receive Claudiximab as intravenous infusion over 2 hours on day 1. Cohorts of 3-6 patients receive escalating doses of Claudiximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no dose-limiting toxicity (DLT) is diagnosed in 3 patients or no more than 1 out of 6 patients exhibits a DLT. After completion of study treatment, patients are followed for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of maximum tolerated dose of claudiximab (Phase I: toxicities as assessed by NCI CTCAE version 3.0)	Four weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Determination of the safety profile	Four weeks
Pharmacokinetic evaluation	Four weeks
Overall tumor response as assessed by RECIST	Four weeks
Evaluation of immunogenicity	Four weeks
Determination of antitumoral efficacy	Four weeks

Collaborators and Investigators

• Sponsor: Ganymed Pharmaceuticals GmbH
• Investigators: Principal Investigator: Martin Schuler, Prof.Dr.med., Innere Klinik (Tumorforschung) Universitätsklinikum Essen Hufelandstr. 55 45122 Essen, GERMANY

Publications and helpful links

General Publications

• Sahin U, Schuler M, Richly H, Bauer S, Krilova A, Dechow T, Jerling M, Utsch M, Rohde C, Dhaene K, Huber C, Tureci O. A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer. Eur J Cancer. 2018 Sep;100:17-26. doi: 10.1016/j.ejca.2018.05.007. Epub 2018 Jun 21.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: May 18, 2009
• First Submitted That Met QC Criteria: May 26, 2009
• First Posted (Estimate): May 27, 2009

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 30, 2017
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Other Study ID Numbers: GM-IMAB-001