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 Anticancer agents
Oesophageal Cancer
Gastric Cancer
Therapy
Biological Therapy
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

Abstract

Aim

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.

Methods

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.

Results

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.

Conclusions

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.

Disclosure

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.