A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: the MONO study.
- Türeci O Ci3 - Cluster of Individualized Immune Intervention, Mainz. Electronic address: tureci@uni-mainz.de.
- Sahin U TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz.
- Schulze-Bergkamen H National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.
- Zvirbule Z Riga East University Hospital, LLC, Riga, Latvia.
- Lordick F University Cancer Center Leipzig, University Medicine Leipzig, Leipzig, Germany.
- Koeberle D Department of Oncology and Hematology, Kantonsspital, St. Gallen, Switzerland.
- Thuss-Patience P Charite University Medicine Berlin, Medical Clinic of Hematology, Oncology and Tumor Immunology, Berlin.
- Ettrich T Department of Internal Medicine I, Ulm University Hospital, Ulm.
- Arnold D Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg.
- Bassermann F Klinikum rechts der Isar, Technische Universität München, Munich.
- Al-Batran SE Nordwest Hospital, Institute of Clinical Cancer Research, University Cancer Center, Frankfurt.
- Wiechen K Klinikum Worms gGmbH, Institute for Pathology, Worms, Germany.
- Dhaene K MD Dhaene Pathology Lab BVBA, Destelbergen, Belgium.
- Maurus D Formerly of Ganymed GmbH (AG), Mainz, Germany.
- Gold M Formerly of Ganymed GmbH (AG), Mainz, Germany.
- Huber C Ci3 - Cluster of Individualized Immune Intervention, Mainz; TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz.
- Krivoshik A Astellas Pharma, Inc., Northbrook, USA.
- Arozullah A Astellas Pharma, Inc., Northbrook, USA.
- Park JW Astellas Pharma, Inc., Northbrook, USA.
- Schuler M West German Cancer Center, University Duisburg-Essen, Essen; German Cancer Consortium (DKTK), Partner site University Hospital Essen, Essen, Germany.
- 2019-06-27
Published in:
- Annals of oncology : official journal of the European Society for Medical Oncology. - 2019
CLDN18.2
IMAB362
gastric cancer
gastro-oesophageal junction adenocarcinoma
zolbetuximab
Adenocarcinoma
Aged
Antibodies, Monoclonal
Drug-Related Side Effects and Adverse Reactions
Esophageal Neoplasms
Esophagogastric Junction
Female
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Stomach Neoplasms
Treatment Outcome
English
BACKGROUND
Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. The first-in-class monoclonal antibody, zolbetuximab (formerly known as IMAB362), binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells.
PATIENTS AND METHODS
Patients with advanced gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50% of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions. At least three patients were enrolled in two sequential cohorts (cohort 1300 mg/m2; cohort 2600 mg/m2); additional patients were enrolled into a dose-expansion cohort (cohort 3600 mg/m2). The primary end point was the objective response rate [ORR: complete and partial response (PR)]; secondary end points included clinical benefit [ORR+stable disease (SD)], progression-free survival, safety/tolerability, and zolbetuximab pharmacokinetic profile.
RESULTS
From September 2010 to September 2012, 54 patients were enrolled (cohort 1, n = 4; cohort 2, n = 6; cohort 3, n = 44). Three patients in cohort 1 and 25 patients in cohorts 2/3 received at least 5 infusions. Antitumour activity data were available for 43 patients, of whom 4 achieved PR (ORR 9%) and 6 (14%) had SD for a clinical benefit rate of 23%. In a subgroup of patients with moderate-to-high CLDN18.2 expression in ≥70% of tumour cells, ORR was 14% (n = 4/29). Treatment-related adverse events occurred in 81.5% (n = 44/54) patients; nausea (61%), vomiting (50%), and fatigue (22%) were the most frequent.
CONCLUSIONS
Zolbetuximab monotherapy was well tolerated and exhibited antitumour activity in patients with CLDN18.2-positive advanced gastric or GEJ adenocarcinomas, with response rates similar to those reported for single-agent targeted agents in gastric/GEJ cancer trials.
CLINICALTRIALS.GOV NUMBER
NCT01197885.
Claudin 18.2 (CLDN18.2) is physiologically confined to gastric mucosa tight junctions; however, upon malignant transformation, perturbations in cell polarity lead to CLDN18.2 epitopes being exposed on the cancer cell surface. The first-in-class monoclonal antibody, zolbetuximab (formerly known as IMAB362), binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells.
PATIENTS AND METHODS
Patients with advanced gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50% of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions. At least three patients were enrolled in two sequential cohorts (cohort 1300 mg/m2; cohort 2600 mg/m2); additional patients were enrolled into a dose-expansion cohort (cohort 3600 mg/m2). The primary end point was the objective response rate [ORR: complete and partial response (PR)]; secondary end points included clinical benefit [ORR+stable disease (SD)], progression-free survival, safety/tolerability, and zolbetuximab pharmacokinetic profile.
RESULTS
From September 2010 to September 2012, 54 patients were enrolled (cohort 1, n = 4; cohort 2, n = 6; cohort 3, n = 44). Three patients in cohort 1 and 25 patients in cohorts 2/3 received at least 5 infusions. Antitumour activity data were available for 43 patients, of whom 4 achieved PR (ORR 9%) and 6 (14%) had SD for a clinical benefit rate of 23%. In a subgroup of patients with moderate-to-high CLDN18.2 expression in ≥70% of tumour cells, ORR was 14% (n = 4/29). Treatment-related adverse events occurred in 81.5% (n = 44/54) patients; nausea (61%), vomiting (50%), and fatigue (22%) were the most frequent.
CONCLUSIONS
Zolbetuximab monotherapy was well tolerated and exhibited antitumour activity in patients with CLDN18.2-positive advanced gastric or GEJ adenocarcinomas, with response rates similar to those reported for single-agent targeted agents in gastric/GEJ cancer trials.
CLINICALTRIALS.GOV NUMBER
NCT01197885.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/annonc/mdz199
- PMID 31240302
- Persistent URL
- https://sonar.ch/global/documents/115596
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