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Clinical Trial
. 2013 Dec 15;119(24):4290-8.
doi: 10.1002/cncr.28353. Epub 2013 Oct 1.

TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for first-line treatment of metastatic colorectal cancer: A randomized phase 1b/2 trial

Charles S Fuchs  1 , Marwan Fakih, Lee Schwartzberg, Allen L Cohn, Lorrin Yee, Luke Dreisbach, Mark F Kozloff, Yong-jiang Hei, Francesco Galimi, Yang Pan, Vincent Haddad, Cheng-Pang Hsu, Antony Sabin, Leonard Saltz
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Free article
Clinical Trial

TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for first-line treatment of metastatic colorectal cancer: A randomized phase 1b/2 trial

Charles S Fuchs et al. Cancer. .
Free article

Abstract

Background: In patients with previously untreated metastatic colorectal cancer (mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety, tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with conatumumab, an investigational, fully human monoclonal IgG1 antibody that specifically activates death receptor 5 (DR5).

Methods: Twelve patients were enrolled in a phase 1b open-label dose-escalation trial of conatumumab with mFOLFOX6/bev; thereafter, 190 patients were randomized 1:1:1 to receive mFOLFOX6/bev in combination with 2 mg/kg conatumumab, 10 mg/kg conatumumab, or placebo. Therapy cycles were repeated every 2 weeks until disease progression or the occurrence of unacceptable toxicity.

Results: In phase 1b, conatumumab with mFOLFOX6/bev was tolerated without apparent added toxicity over mFOLFOX6/bev alone. In phase 2, conatumumab with mFOLFOX6/bev did not confer a benefit in progression-free survival when compared with placebo with mFOLFOX6/bev. Toxicity was similar in all treatment arms. Following treatment, similar increases in circulating caspase-3 levels were observed in all arms.

Conclusions: Conatumumab with mFOLFOX6/bev did not offer improved efficacy over the same chemotherapy with placebo in first-line treatment of patients with mCRC. These data do not support further development of conatumumab in advanced CRC.

Trial registration: ClinicalTrials.gov NCT00625651.

Keywords: AMG 655; FOLFOX; bevacizumab; conatumumab; death receptor 5 agonist; metastatic colorectal cancer.

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