New Enzalutamide Data in Triple-Negative Breast Cancer Presented at the 2015 American Society of Clinical Oncology Annual Meeting

Medivation, Inc.

today announced that data from a Phase 2 study evaluating the investigational use of enzalutamide as a single agent for the treatment of advanced androgen receptor (AR) positive, triple-negative breast cancer (TNBC) were presented during an oral abstracts session at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The study met its primary endpoint and the abstract was also selected to be featured in the upcoming 'Best of ASCO' meetings. The Phase 2 open label single arm, multicenter trial enrolled 118 women with advanced TNBC in two stages. The primary endpoint of the trial was clinical benefit rate at 16 weeks (CBR16), defined as the proportion of women with a complete response (CR), partial response (PR) or stable disease for at least 16 weeks. Two patient populations were evaluated in this study: the Evaluable patient population had at least 10 percent of the cells in their primary tumor sample test positive for the AR and had at least one follow up tumor assessment, while the Intent-To-Treat population (ITT) received at least one dose of enzalutamide and their breast cancer had any amount of AR immunohistochemistry staining present. 75 patients met the criteria for the Evaluable population and a total of 118 patients were included in the ITT population. There was no limit to the number of prior treatments received. In the 75 Evaluable patients, CBR16 was achieved in 35% (95% CI: 24-46) including six CR/PR (8%). Clinical benefit rate at ≥ 24 weeks (CBR24) was achieved in 29% (95% CI: 20-41). The median progression-free survival (PFS) was 14.7 weeks (95% CI: 8.1-19.3). In the ITT population, CBR16 was achieved in 25% (95% CI: 17-33) including seven CR/PR (6%). CBR24 was achieved in 20% (95% CI: 14-29). Median PFS was 12.6 weeks (95% CI: 8.1-15.7). Data collected in this study enabled the development of a novel genomic assay. The diagnostic assay, which was also introduced during a poster abstract session at ASCO, was assessed for its ability to identify patients who may benefit from enzalutamide. Approximately 50 percent of the ITT population were diagnostic positive and exploratory data according to this methodology were as follows: In the ITT, 39% (95% CI: 27-53) of patients with diagnostic positive AR TNBC achieved CBR16 and 36% achieved CBR24 (95% CI: 24-49), whereas 11% (95% CI: 5-21) of patients with diagnostic negative AR TNBC achieved CBR16 and only 6% (95% CI, 2-16) achieved CBR24. mPFS was 16.1 weeks (95% CI: 13.3, 27.4) compared with 8.1 weeks (95% CI: 7.4, 12.6), respectively. Diagnostic positive AR TNBC patients treated with enzalutamide as their first or second line of treatment in the ITT population demonstrated a median PFS of 40.4 weeks (95% CI: 16.1- not yet reached) compared with 8.9 weeks (95% CI: 7.3, 15.7) in patients with diagnostic negative AR TNBC disease. A multi-covariate Cox-proportional hazards model of PFS demonstrated that the nominal p-value for this diagnostic covariate (positive vs. negative) is p=0.0042. The number of prior therapies (0-1 vs. ≥ 2) was the only other variable that significantly and independently associated with outcome by the multi-covariate Cox-proportional hazards model of PFS, with a nominal p-value of p=0.0010. Age (≥ 65 vs < 65 years), disease-free interval and immunohistochemistry staining for AR (≥ 10% vs < 10%) were not significant. At the time of the analysis for PFS, median overall survival in patients in the ITT population with diagnostic positive AR TNBC treated with enzalutamide had not yet been reached (95% CI: 55.4-not yet reached), compared with 32.1 weeks in patients with diagnostic negative AR TNBC (95% CI: 20.7-48.3). The most common (reported in ≥10%) related adverse events in the ITT were fatigue (34%), nausea (25%), decreased appetite (13%), diarrhea and hot flush (10% each). "I am extremely encouraged by the results of this study, as there is an urgent need for new therapies that have the potential to stabilize disease in women with advanced triple negative breast cancer, for which the only option is chemotherapy," said Tiffany A. Traina, M.D., principal investigator of the study and medical oncologist of the Breast Medicine Service, Memorial Sloan Kettering Cancer Center. "The progression free survival exceeding nine months as observed in first and second line patients with diagnostic positive AR TNBC is compelling and I look forward to results from further studies of enzalutamide that evaluate those patients most likely to benefit from this hormonally targeted therapy." XTANDI is not approved for the treatment of advanced androgen receptor positive, triple-negative breast cancer. The diagnostic referred to in this press release is neither approved nor commercially available. Best of ASCO The 'Best of ASCO' Meetings condense the most cutting-edge science and education from the world's premier oncology event, the ASCO Annual Meeting, into a two-day program. The abstracts chosen for presentation and discussion reflect the foremost research and strategies in oncology that have the greatest potential to directly impact patient care. About the Phase 2 Study The Phase 2 open label, single-arm study was initiated in June 2013 and completed enrollment in July 2014. 118 patients were enrolled in 2 Stages at sites in the United States, Canada and Europe. The primary endpoint of the trial is clinical benefit rate, defined as the proportion of patients in the Evaluable population with a best response of complete response, partial response or stable disease at ≥ 16 weeks. All patients received enzalutamide at a dose of 160 mg to be taken orally once daily. Rejection of the null hypothesis required that greater than or equal to 9 of 62 (15%) Evaluable patients achieved CBR16.