Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer
Mené sur 63 patients atteints d’un cancer colorectal non résécable et réfractaire (âge médian : 58 ans), cet essai de phase II évalue l’efficacité, du point de vue de la survie globale, et la toxicité de l’ensituximab, un nouvel anticorps monoclonal ciblant un variant du gène MUC5AC
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.