In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 4080-4080
Abstract:
4080 Background: IMAB362 is a monoclonal antibody targeting isoform 2 of the tight junction component claudin 18 (CLDN18.2), a tumor-selective antigen frequently expressed in several types of epithelial adenocarcinomas. Preclinically, IMAB362 exerts its antitumor activity by ADCC, CDC, induction of apoptosis and inhibition of cell proliferation. Methods: Patients with treatment-refractory, metastatic gastroesophageal adenocarcinomas with CLDN18.2-positive tumors as determined by immunohistochemistry were enrolled in two clinical trials of IMAB362 monotherapy. A phase I inter-patient single dose escalation study (n=15, 5 dose groups from 33 mg/m² to 1000 mg/m² with 3 patients each, follow-up 4 weeks) was conducted followed by a phase II study (n=34, 300 mg/m 2 [n=4] and 600 mg/m 2 [n=30]) administered every two weeks for 5 courses, imaging in week 11. Patients with disease control allowed to continue IMAB362 therapy until progression. Analysis of the phase II trial is ongoing. Results: In the phase I trial, all dose levels of IMAB362 were generally well tolerated. Nausea and vomiting were the most common adverse events (AEs). No dose limiting toxicity was observed at single doses up to 1,000 mg/m². Based on pharmacokinetic considerations and preclinical dose/response data, the recommended doses for the phase II multidose trial was 600 mg/m². In the phase II study, 34 patients were evaluable for safety. No grade 4 AEs occurred, grade 3 AEs were vomiting (n=8, 24%), nausea (n=4, 12%) and hypersensitivity (n=1, 3%). As of January 2013, 31 patients were evaluable for efficacy analysis. Four patients had achieved a confirmed partial response, and eight patients had disease stabilization (ORR=13%, DCR=39%). The longest observed response duration thus far was 40 weeks. Conclusions: IMAB362 antibody therapy of patients with advanced CLDN18.2-positive gastroesophageal adenocarcinomas is safe and well tolerated. Early evidence for antitumoral activity was observed in the phase II trial. Further clinical evaluation of IMAB362 in patients with CLDN18.2 tumors is warranted. Clinical trial information: NCT01197885.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.4080
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
Bookmarklink
