Final results from an open-label, randomised, phase II study of adecatumumab (MT201), a fully human anti-EpCAM antibody, in patients with metastatic breast cancer

Abstract

3588 Background: High-level expression of the epithelial cell adhesion molecule (EpCAM) has been associated with unfavourable prognosis in various cancers. Adecatumumab was developed as a low-affinity IgG1 antibody targeting EpCAM-positive cancer cells. Methods: EpCAM-positive metastatic breast cancer patients without CNS metastases, with no indication for trastuzumab were eligible; an initial restriction to a maximum of one previous chemotherapy for metastatic disease was subsequently removed. 109 EpCAM- positive patients were enrolled. Patients were stratified into high- and low-level EpCAM expression (n = 74 and 35, respectively) according to immuno-histochemistry testing, and subsequently randomised to receive either high-dose (6 mg/kg/q2w) or low-dose (2 mg/kg/q2w) adecatumumab (n = 54 and 55, respectively). Primary endpoint was clinical benefit rate (CBR = objective response + stable disease) at week 24 with secondary parameters exploring time to progression (TTP) and safety. Results: The primary endpoint (CBR at week 24: >25%) was not met in any of the 4 groups according to central radiological review. Exploratory analyses of the Kaplan-Meier curves, however, showed a lower probability for tumor progression in patients receiving high dose adecatumumab (HR: 0.67 [0.47–0.94]; p=0.047). A similar trend was also observed in patients with high-level EpCAM expression (HR: 0.71 [0.49–1.03]; p=0.116). Further (retrospective) analysis using more stringent criteria for the definition of high-level EpCAM expression indicated an inverse correlation of staining intensity and frequency with probability of progression. An increased incidence of CTC grade 1 and 2 AE was found in the high-dose group with main side effects being gastrointestinal and constitutional symptoms. Conclusions: The observation of dose- and target-dependent activity of adecatumumab warrants further investigation. Definition of the optimum dose and regimen as well as exploration of the predictive value of EpCAM testing will be key in future development. No significant financial relationships to disclose.