A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer
| Autor: | Magdalena Jadwiga Utsch, Anna Krilova, Özlem Türeci, Martin Schuler, Karl Dhaene, Markus Jerling, Christoph Rohde, Stefan Bauer, Tobias Dechow, Ugur Sahin, Heike Richly, Christoph Huber |
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| Přispěvatelé: | Supporting clinical sciences, Experimental Pathology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cancer Research medicine.medical_specialty Time Factors Esophageal Neoplasms Maximum Tolerated Dose medicine.medical_treatment Medizin Gastroenterology Antibodies Monoclonal/administration & dosage 03 medical and health sciences 0302 clinical medicine Antineoplastic Agents Immunological Pharmacokinetics Antineoplastic Agents Immunological/administration & dosage Stomach Neoplasms Internal medicine Germany medicine Humans Drug Dosage Calculations Adverse effect Infusions Intravenous Aged business.industry Cancer Antibodies Monoclonal Esophagogastric Junction/drug effects Immunotherapy Middle Aged medicine.disease Latvia ddc 030104 developmental biology Treatment Outcome Oncology Tolerability Response Evaluation Criteria in Solid Tumors 030220 oncology & carcinogenesis Toxicity Disease Progression Female Stomach Neoplasms/drug therapy Esophagogastric Junction Esophageal Neoplasms/drug therapy business Progressive disease |
| ISSN: | 0090-9025 |
| DOI: | 10.1016/j.ejca.2018.05.007 |
| Popis: | Introduction IMAB362 (Zolbetuximab) is a chimeric monoclonal antibody that binds to Claudin-18.2, a target antigen specific to cancer cells. In vitro, IMAB362 mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity; thus, IMAB362 may serve as a potent, targeted immunotherapeutic agent. Methods This first-in-human phase I study enroled adult patients (N = 15) with advanced gastric or gastro-oesophageal junction cancer into five sequential single dose-escalation cohorts (33, 100, 300, 600, and 1000 mg/m2) following a 3 + 3 design. Safety/tolerability, including determination of maximum tolerated dose and recommended phase II dose, were the primary objectives; secondary objectives included assessment of the IMAB362 pharmacokinetic profile, immunogenicity, and antitumour activity (assessed by Response Evaluation Criteria in Solid Tumors v1.0). Results IMAB362 was generally well tolerated at all doses, with gastrointestinal toxicities being the most commonly observed treatment-related adverse events. As dose-limiting toxicity was not observed within 4 weeks of treatment, a maximum tolerated dose was not established. The pharmacokinetic profile of IMAB362 appeared to be proportional across the dose range; and mean half-life ranged from 13 to 24 d. While most patients showed progressive disease at weeks 4-5 after a single intravenous IMAB362 infusion, one patient in the 600 mg/m2 dose group achieved and maintained stable disease for approximately 2 months postinfusion. Conclusions Findings from this study demonstrate that IMAB362 is generally well tolerated and support further evaluation in patients with gastric/gastro-oesophageal junction cancer. Clinical trial registry ClinicalTrials.gov, Identifier NCT00909025. |
| Databáze: | OpenAIRE |
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