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Cancer Chemother Pharmacol. 2011 Sep;68(3):733-41. doi: 10.1007/s00280-010-1544-1. Epub 2010 Dec 16.

Phase 1 study of conatumumab, a pro-apoptotic death receptor 5 agonist antibody, in Japanese patients with advanced solid tumors.

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1
Gastrointestinal/Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. todoi@east.ncc.go.jp

Abstract

PURPOSE:

Conatumumab is a fully human monoclonal agonist antibody against human death receptor 5 (DR5). The primary objectives of this phase 1 study were to assess the safety, tolerability, and pharmacokinetics (PK) of conatumumab in Japanese patients with advanced solid tumors.

METHODS:

This is an open-label ascending dose study with a starting dose level of 3 mg/kg. Subsequent doses of 10 and 20 mg/kg were planned. Six patients were enrolled into 1 of 3 dose cohorts (3, 10, or 20 mg/kg) of conatumumab administered intravenously once every 2 weeks as a single agent. No conatumumab was administered on day 43 to allow the assessment of terminal PK parameters. The primary endpoints were the incidence of dose-limiting toxicities (DLTs) and assessment of PK parameters of conatumumab.

RESULTS:

Eighteen patients received at least 1 dose of conatumumab. There were no DLTs observed as defined in the protocol. No patients had an adverse event leading to conatumumab discontinuation. Conatumumab demonstrated dose-linear kinetics. A best response of stable disease was reported in nine patients. Monocytes were found to express DR5 and showed a high degree of conatumumab receptor occupancy after treatment at all dose levels.

CONCLUSIONS:

Conatumumab administered up to 20 mg/kg once every 2 weeks was well tolerated in Japanese patients with advanced solid tumors. Adverse events and PK in these patients were similar to those in the first in human (FIH) study.

PMID:
21161528
DOI:
10.1007/s00280-010-1544-1
[Indexed for MEDLINE]

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