Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer

Abstract

Purpose: Patients with metastatic colorectal cancer (CRC) refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric monoclonal antibody targeting a variant of MUC5AC with specificity to CRC. Patients and Methods: Single arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory cancer who expressed MUC5AC antigen in tumor tissue. Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended phase II dose (RP2D). A minimum sample size of 43 patients was required based on the assumption that ensituximab would improve median overall survival by 7 months using a one-sided significance level of 10% and 80% power. Written informed consent was obtained from all patients. Results: Sixty-three patients with advanced, refractory CRC were enrolled and 53 subjects were treated in phase 2 arm. Median age was 58 years and 46% of the patients were female. Among 57 evaluable patients, median OS was 6.8 months. No responses were observed, and stable disease was achieved in 21% of the patients. The most common treatment related adverse events at RP2D included fatigue (38%), anemia (30%), nausea (15%), vomiting (11%), increased bilirubin (9%), constipation (8%), decreased appetite (6%) and diarrhea (6%). Serious adverse events at least possibly related to ensituximab occurred in 4 patients and included anemia, nausea, increased bilirubin and hypoxia. No patients discontinued treatment due to drug related adverse events. Conclusions: Ensituximab was well tolerated and demonstrated modest antitumor activity in patients with heavily pretreated refractory CRC.