636P - Efficacy and safety of multiple doses of IMAB362 in patients with advanced gastro-esophageal cancer: Results of a phase II study

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Oesophageal Cancer
Gastric Cancer
Presenter Tanja Trarbach
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors T. Trarbach1, M. Schuler2, Z. Zvirbule3, F. Lordick4, A. Krilova5, U. Helbig6, H. Schulze-Bergkamen7, P.C. Thuss-Patience8, G. Wichert9, W. Schmiegel10, S. Bauer11, C. Müller12, S. Al-Batran13, C. Huber14, D. Maurus15, M. Kühnle15, U. Sahin14, Ö. Türeci16
  • 1Gastroenterology, West German Cancer Center, 45147 - Essen/DE
  • 2Department Of Medical Oncology, West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 3Oncology, Riga Eastern Clinical University Hospital, Riga/LV
  • 4University Cancer Center Leipzig, University of Leipzig, 04103 - Leipzig/DE
  • 5Oncology, Liepaja Piejuras Hospital, Liepaja/LV
  • 63rd Medical Department, Hematology And Oncology, Klinikum Braunschweig, Braunschweig/DE
  • 7Department For Medical Oncology, Nationales Zentrum f, DE-69120 - Heidelberg/DE
  • 8Klinik Mit Schwerpunkt H, Charite, DE-13353 - Berlin/DE
  • 9Gastroenterology, Schön Klinik Hamburg Eilbeck, Hamburg/DE
  • 10Knappschaftskrankenhaus, Ruhr University BochumMedizinische Universit, DE-44892 - Bochum/DE
  • 11Gastroenterology, Caritas Hospital Lebach, Lebach/DE
  • 12Clinical Research, Ganymed AG, Mainz/DE
  • 13Medizinische Klinik Ii Für Hämatologie Und Onkologie, Institut für klinische Forschung (IKF) am Krankenhaus Nordwest - UCT, Universitäres Centrum für Tumorerkrankungen Frankfurt, 60488 - Frankfurt am Main/DE
  • 14Tron, TRON – Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz/DE
  • 15Translational Research, Ganymed AG, Mainz/DE
  • 16Ceo, Ganymed AG, Mainz/DE



IMAB362 is a monoclonal antibody specifically targeting claudin 18 isoform 2 (CLDN18.2), which is expressed on gastric cancer cells, whereas it is only present on a fraction of healthy stomach cells. This may reduce the risk of target-related side effects. Single-agent IMAB362 appears safe in patients with advanced gastro-esophageal cancer (GEC) based on data from a phase I trial.


This international, multicenter, non-randomized phase IIa study (NCT01197885) investigated the efficacy and safety of repeated doses of IMAB362 (300 and 600 mg/m2) in patients with metastatic, refractory/recurrent, CLDN18.2-positive GEC (i.e. cancer of the stomach, the lower esophagus and the GE junction). Patients received bi-weekly IMAB362 at 300 or 600 mg/m2 as 2-hour IV infusion. Response rate (RECIST criteria), progression-free-survival (PFS) and safety (NCI-CTCAE v3.0) were assessed. Pharmacokinetics (PK) were determined and an extensive biomarker program was conducted.


54 patients were included in this study: 4 patients received 300 mg/m2 and 50 patients 600 mg/m2. The median age was 62 (range 45–66) years in the 300 mg/m2 and 60 (range 35–77) years in the 600 mg/m2 dose group. More than 50% of patients had received chemotherapy in the 6 months preceding this study. The full analysis set comprised 40 patients (all in 600 mg/m2 group) including 9 patients who continued to receive IMAB362 following the study period. The response rate was 10% and the disease control rate was 30% (best observed response: PR, n = 4 and SD, n = 8). Median PFS was 102 days (95% CI, 70–146 days). All observed adverse events were of grade 1–3, adverse events of grade 4/5 did not occur. Nausea and vomiting were the most common study drug-related adverse events in 31 (n = 8 with grade 3 nausea) and 27 (n = 13 with grade 3 vomiting) of 54 patients, respectively. PK supports 3-weekly IV dosing.


Clinical efficacy of IMAB362 at repeated doses was observed in several patients. IMAB362 at 600 mg/m2 appears safe and feasible in patients with advanced late-stage GEC. Hence, IMAB362 may provide a promising new treatment option for this patient population and further clinical evaluation is ongoing.


U. Sahin: Inventor of patents on CLDN18.2; Ö. Türeci: Employed by Ganymed Pharmaceuticals AG and inventor of patents on CLDN18.2. All other authors have declared no conflicts of interest.