Phase 1 Study of IMAB362 with immunomodulation in patients with advanced gastric cancer

FAST: An international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma.

LBA4001 Background: Claudin18.2 (CLDN18.2) is a tight junction protein expressed by several cancers including gastric and GEJ adenocarcinoma. IMAB362 is a chimeric monoclonal antibody that mediates specific killing of CLDN18.2-positive cancer cells by activation of immune effector mechanisms. IMAB362 has demonstrated single-agent activity and was safe and tolerable in patients (pts) with pretreated gastric cancer. Methods: Pts with advanced/recurrent gastric and GEJ cancer were centrally evaluated for CLDN18.2 expression by IHC (validated CLAUDETECT18.2 Kit). Eligible pts had a CLDN18.2 expression of ≥ 2+ in ≥ 40% tumor cells, an ECOG PS of 0–1 and were not eligible for trastuzumab. Pts we…

Expression of Claudin 18.2 and HER2 in gastric, gastroesophageal junction, and esophageal cancers : Results from the FAST study

4038 Background: Claudin 18.2 (CLDN18.2), a gastric mucosa tight junction protein, is aberrantly expressed in various cancers. In the FAST Phase 2 trial (NCT01630083), IMAB362, an anti-CLDN18.2 monoclonal antibody, administered in combination with EOX chemotherapy, prolonged survival compared to EOX alone in patients with advanced/recurrent gastric, gastroesophageal junction (GEJ), and esophageal cancers ineligible for trastuzumab. The aim of the present analysis was to assess tumor CLDN18.2 expression and co-expression with HER2 in the FAST population. Methods: Tumor tissue samples from patients screened for inclusion into the FAST trial were analyzed for CLDN18.2 expression using a CE-ma…

220O Claudin 18.2 - a novel treatment target in the multicenter, randomized, phase II FAST study, a trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without the anti-CLDN18.2 antibody IMAB362 as 1st line therapy in advanced gastric and gastroesophageal junction (GEJ) cancer

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

Abstract 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 …

Final results of the FAST study, an international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without the anti-CLDN18.2 antibody IMAB362 as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma

Background: IMAB362, a chimeric monoclonal antibody that mediates specific killing of cancer cells expressing the tight junction protein Claudin18.2 (CLDN18.2) by activation of immune effector mechanisms, has demonstrated single-agent activity and tolerability in patients ( pts) with heavily pretreated gastric cancer. Methods: Pts with advanced/recurrent gastric and GEJ cancer were centrally evaluated for CLDN18.2 expression by immunohistochemistry (CLAUDETECT® 18.2 Histology Kit). Eligible pts had a CLDN18.2 expression of ≥2+ in ≥40% tumor cells, an ECOG PS of 0–1 and were not eligible for trastuzumab. Pts were randomized 1:1 to first-line EOX (epirubicin 50 mg/m2 and oxaliplatin 130 mg/m2…

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

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 th…