A randomized, phase II trial of AEZS-108 in chemotherapy refractory triple-negative (ER/PR/HER2-negative) LHRH-R positive metastatic breast cancer

TPS11124 Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is clinically negative for expression of estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2 (HER2). It is characterized by its unique molecular profile, aggressive behavior, distinct patterns of metastasis, and lack of commercially available targeted therapies. Chemotherapy has been the mainstay of treatment for women with TNBC, but this current standard-of-care is suboptimal. AEZS-108 is an LHRH-cytotoxic hybrid drug whose rational design covalently couples the carrier D-Lys6-LHRH (an LHRH agonist) to the cytotoxic doxorubicin radical. Because LHRH receptors are expressed in a majority of TNBC, AEZS-108 represents a novel way to selectively deliver cytotoxic chemotherapy in patients with TNBC via a new therapeutic target. Methods: In this open label randomized two-arm multicenter phase II study, patients will be randomized in a 1:1 ratio into one of the two treatment arms: AEZS-108 (267 mg/m2 every 21 calendar days) [Arm A] or SSC (standard single agent cytotoxic chemotherapy [Arm B]) at discretion of treating oncologist cycled every 21 calendar days. Stratified randomization will be used with number of prior lines of therapies (1-2 vs. >2), ECOG performance status 0-1 vs. 2, and liver metastases (absent vs. present). Analysis of the main study endpoint, TTP, will follow a group sequential design with two interim analyses, including the final analysis. O’Brien Fleming stopping boundaries will be used. The primary endpoint is to evaluate the median time to progression (TTP) of AEZS-108 in patients with chemotherapy resistant advanced TNBC treated with AEZS-108 in relation to patients receiving standard single agent cytotoxic chemotherapy. Secondary endpoints include: overall response, clinical benefit, duration of response, overall survival, toxicity profile and quality of life (QoL). Clinical trial information: NCT01698281.