61ATTAINMENT: A modular phase lb trial of MDX-124, a first-in-class annexin-A1 targeting antibody in patients with advanced solid tumors including cholangiocarcinoma.
Daniel H Palmer, Stefan N Symeonides, Alan Christie, Emily Spiers, Chiara Braconi, Mairéad G McNamara, Debashis Sarker, Fiona C Dempsey, Scott J Crichton, Colin Tennant, Christopher B Wood, Lisa C Yule, Sarah P BlagdenAbstract
Background and Objectives
Annexin-A1 overexpression in tumors correlates with poor prognosis in several malignancies, including cholangiocarcinoma, making it a novel therapeutic target. MDX-124 is a first-in-class monoclonal antibody that targets annexin-A1. In preclinical models, MDX-124 significantly inhibits tumor growth and the development of metastases, induces antibody-dependent cellular cytotoxicity and has demonstrated synergy with chemotherapeutics.
Method
ATTAINMENT is a modular, multi-arm, phase lb study of MDX-124 enrolling adult patients with solid tumors likely to overexpress annexin-A1. Module 1 is a single agent dose escalation using a BOIN (Bayesian Optimal Interval) design, with an expansion cohort in which MDX-124 is administered Q2W at doses ranging from 1-30 mg/kg with a 21-day DLT period until disease progression or intolerance. Module 2 will evaluate MDX-124 as monotherapy and in combination with standard of care (SOC) therapies in indication-specific arms using a modified 3 + 3 design, beginning with cholangiocarcinoma. The primary objective of Module 2 is to assess the safety and tolerability of MDX-124 in selected tumor types when administered as a single agent or in combination with SOC therapies. Secondary objectives are to characterize PK and assess evidence of anti-tumor activity. Responses are evaluated according to RECIST v1.1. Adverse events are graded using CTCAE. Tumor and immunological biomarkers are being evaluated as exploratory endpoints.
Results and Conclusion
Preliminary data from the Module 1 dose escalation indicate promising safety, tolerability, and anti-tumor activity of MDX-124 in cholangiocarcinoma and other tumor types. Module 2 is currently further exploring encouraging monotherapy activity of MDX-124 in cholangiocarcinoma. Clinical trial information: ISRCTN78740398.