A Randomized, Double-blind, Placebo-controlled Phase 2 Study of Ontuxizumab (MORAb-004) in Patients with Chemorefractory Metastatic Colorectal Cancer

Purpose: The purpose of this study was to evaluate the safety and efficacy of ontuxizumab (MORAb-004), a monoclonal antibody that interferes with endosialin (tumor endothelial marker-1 [TEM-1]) function, in patients with chemorefractory metastatic colorectal cancer and to identify a responsive patient population based on biomarkers. Design: This was a randomized, double-blind, placebo-controlled, Phase 2 study. Patients were randomly assigned in a 2:1 ratio to receive weekly intravenous ontuxizumab (8 mg/kg) or placebo plus best supportive care (BSC) until progression or unacceptable toxicity. Tissue and blood biomarkers were evaluated for their ability to identify a patient population that was responsive to ontuxizumab. Results: A total of 126 patients were enrolled. No significant difference between the ontuxizumab and placebo groups was evident for the primary endpoint of progression-free survival (PFS), with a median PFS of 8.1 weeks in each group (hazard ratio of 1.13; 95% confidence interval: 0.76, 1.67; P=0.53). There were no significant differences between groups for overall survival (OS) or overall response rate (ORR). The most common treatment-emergent adverse events (TEAEs) in the ontuxizumab group (vs the placebo group, respectively) were fatigue (53.7% vs 47.5%), nausea (39.0% vs 35.0%), decreased appetite (34.1% vs 27.5%), and constipation (28.0% vs 32.5%). The most common Grade 3/4 TEAE in the ontuxizumab group vs placebo was back pain (11.0% vs 0%). No single biomarker clearly identified patients responsive to ontuxizumab. Conclusion: No benefit with ontuxizumab monotherapy compared with placebo for clinical response parameters of PFS, OS, or ORR was demonstrated. Ontuxizumab was well tolerated.

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