Medivation's business is built on the identification and rapid development of product candidates that have the potential to improve the standard of care in human diseases.
Ongoing Clinical Studies
STRIVE PROSPER EMBARK PLATO NEOADJUVANT
ER+ or PgR+ &
AR+ HER2 Amplified
Medivation, in collaboration with Astellas, is currently developing enzalutamide for multiple stages of prostate cancer and for breast cancer.
The STRIVE trial was initiated in August 2012. The trial is evaluating enzalutamide head-to-head versus bicalutamide, the leading marketed anti-androgen drug, in approximately 400 pre-chemotherapy CRPC patients. The randomized, double-blind trial is enrolling both metastatic and non-metastatic patients and is being conducted primarily in the United States. The primary endpoint in the study is progression-free survival.
The first patient was enrolled in the Phase 3 PROSPER trial in December 2013. The trial will evaluate the safety and efficacy of enzalutamide in patients with non-metastatic CRPC. PROSPER will enroll a high-risk subgroup of patients with prostate cancer who are progressing despite androgen deprivation therapy, but who are asymptomatic with no prior or present evidence of metastatic disease. The Phase 3 randomized, double-blind, placebo-controlled, multi-national trial plans to enroll approximately 1,500 patients with non-metastatic CRPC. The primary endpoint of the trial is metastasis free survival.
The first patient was initiated in the Phase 3 EMBARK trial in January 2015. The trial will evaluate the efficacy and safety of enzalutamide in patients with high-risk, hormone-sensitive, non-metastatic prostate cancer that has biochemically recurred (rising prostate-specific antigen, or PSA level) following surgery and/or radiation. This trial will determine if enzalutamide can delay or prevent the development of metastatic prostate cancer in high-risk men with a rapidly rising PSA. The primary endpoint of the trial is metastasis-free survival. The trial is designed to enroll approximately 1,860 patients.
PLATOThe Phase 4 PLATO trial was initiated in November 2013. The trial will evaluate the efficacy and safety of continued treatment with enzalutamide plus abiraterone acetate and prednisone as compared to treatment with abiraterone acetate and prednisone alone in patients with chemotherapy-naïve metastatic prostate cancer whose disease has progressed following enzalutamide therapy. The purpose of the trial is to help determine the potential clinical benefit of extending time on enzalutamide treatment by adding an additional therapy in patients with progressive chemotherapy-naïve metastatic prostate cancer. The global randomized, double-blind, placebo-controlled trial is designed to enroll approximately 500 chemotherapy-naïve patients with mCRPC. The primary endpoint of the trial is progression-free survival.
The neoadjuvant trial was initiated in May 2012. The open-label trial is evaluating enzalutamide, either in combination with leuprolide and dutasteride or alone, as neoadjuvant therapy in approximately 50 men who have been diagnosed with prostate cancer but not yet undergone prostatectomy. Men in this trial will receive enzalutamide for six months before prostatectomy, and then undergo surgery. The removed prostates will then be examined pathologically to determine whether any cancer remains. The primary endpoint in this trial is pathologic complete response rate.
In April 2012, we and Astellas expanded the clinical development of enzalutamide to include a new indication, breast cancer. We are enrolling patients in an open label Phase 1 study designed to evaluate the safety and tolerability of enzalutamide in approximately 60 metastatic breast cancer patients who have failed at least two prior hormonal therapies.
In June 2013, we initiated patient enrollment in a Phase 2 clinical trial evaluating enzalutamide as a single agent for the treatment of advanced, androgen receptor positive, triple-negative breast cancer (TNBC). TNBC is a type of cancer which is not driven by the three most commonly targeted receptors in breast cancer: estrogen, progesterone and HER2. The Phase 2 open label, single-arm, multicenter trial plans to enroll approximately 80 patients with AR-positive, TNBC 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 with a best response of complete response, partial response or stable disease at ≥ 16 weeks. All patients will receive enzalutamide at a dose of 160 mg to be taken orally once daily. Click for Press Release.
ER+ or PgR+ & HER2 normal
In December 2013, we initiated a Phase 2 clinical trial evaluating enzalutamide in combination with exemestane in women with advanced breast cancer that is estrogen receptor positive (ER+) or progesterone receptor positive (PgR+) and human epidermal growth factor receptor 2 (HER2) normal. The Phase 2 randomized, double-blind, placebo-controlled, multicenter trial will assess 240 patients in two parallel cohorts of 120 patients each. The first cohort will enroll patients who have not previously received hormonal treatment for advanced breast cancer. The second cohort will enroll patients who have previously progressed following one hormonal treatment for advanced disease. The primary endpoint of the trial is progression-free survival in all patients and in the subset of patients whose tumor expresses the androgen receptor.
AR+ and HER2 Amplified
In August 2014, we initiated start up activities in a Phase 2 trial evaluating the safety and efficacy of adding enzalutamide to trastuzumab in approximately 80 patients with metastatic or locally advanced breast cancer that is androgen-receptor positive (AR+), human epidermal growth factor receptor 2 (HER2) amplified, and estrogen-receptor negative (ER-) or progesterone receptor negative (PgR-) whose disease has previously progressed on trastuzumab. The primary endpoint of the trial is clinical benefit rate defined as complete response or partial response or stable disease ≥ 24 weeks. The goal of the study is to determine whether enzalutamide will provide any incremental benefit for women who have progressed on trastuzumab.
Completed Enzalutamide Studies
In November 2010, we completed enrollment in a randomized, double-blind, placebo-controlled, Phase 3 trial evaluating enzalutamide (160 mg/day) versus placebo in 1,199 men with advanced prostate cancer who were previously treated with docetaxel-based chemotherapy. On November 3, 2011, data was reported from an interim analysis. In the trial, enzalutamide successfully met the study's pre-specified interim efficacy stopping criteria, demonstrating a clinically meaningful and statistically significant (p < 0.0001) improvement in overall survival compared to placebo. As a result, the IDMC recommended that AFFIRM be stopped early and men who received placebo be offered MDV3100. Click for Press Release. Additional data from the Phase 3 trial were presented at the American Society of Clinical Oncology 2012 Genitourinary Cancers Symposium. Click for Press Release. Data from this trial were published in The New England Journal of Medicine in 2012.
The PREVAIL trial was a randomized, double-blind, placebo-controlled trial, evaluating enzalutamide (160 mg once daily) as compared to placebo in patients with pre-chemotherapy mCRPC. PREVAIL included patients who progressed following treatment with an LHRH analog drug only, as well as patients who have progressed following treatment with both an LHRH analog drug and an anti-androgen drug. On October 22, 2013, the Independent Data Monitoring Committee informed Medivation and Astellas of positive results from a planned interim analysis of PREVAIL. Given the observed benefits in the trial's co-primary endpoints of overall survival and radiographic progression-free survival, and considering the observed safety profile, the IDMC concluded enzalutamide demonstrated a favorable benefit-risk ratio. The IDMC recommended the study be stopped and patients treated with placebo be offered enzalutamide. Click for Press Release. Additional data from the Phase 3 PREVAIL results was presented at the American Society of Clinical Oncology 2014 Genitourinary Cancers Symposium. Click for Press Release. Data from this study were published in the New England Journal of Medicine in 2014.
The Phase 2 trial evaluated enzalutamide head-to-head versus bicalutamide in pre-chemotherapy CRPC patients. The randomized, double-blind trial enrolled only metastatic patients. The primary endpoint in the study was progression-free survival. We completed patient enrollment in the TERRAIN trial in July 2013. Data from the study were announced in January 2015, with enzalutamide achieving its primary endpoint in the study. Click for Press Release.
Phase 1-2 Trial
In December 2008, we completed enrollment in an open-label Phase 1-2 clinical trial of enzalutamide in patients with metastatic castration-resistant prostate cancer. We enrolled 140 patients in seven dose groups, ranging from 30 mg/day to 600 mg/day. Of the 140 patients, 75 had previously failed docetaxel-based chemotherapy and 65 were chemotherapy-naïve. All 140 patients also had failed at least one line of prior hormonal therapy. The trial endpoints included safety, tolerability, pharmacokinetics, circulating tumor cell, or CTC, counts, PSA levels, radiographic change in soft tissue and bony metastases, and time to progression. Data from this trial were published in The Lancet in 2010.
In January 2012, we completed enrollment in an open label Phase 1-2 clinical trial of enzalutamide in hormone-naïve patients. The study enrolled 67 patients, and was the first time we had dosed enzalutamide in men who had not yet undergone prior hormone therapy. Data from this trial were reported at the 2013 Genitourinary Cancers Symposium in February.