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, 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, Charles S Fuchs, 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
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.
© 2013 American Cancer Society.
Source: PubMed