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RESEARCH PRODUCT

Efficacy and Safety of Multiple Doses of Imab362 in Patients with Advanced Gastro-Esophageal Cancer: Results of a Phase Ii Study

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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; O. Tureci: Employed by Ganymed Pharmaceuticals AG and inventor of patents on CLDN18.2. All other authors have declared no conflicts of interest.