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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Claudiximab


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Claudiximab<br> | Drug: Claudiximab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |