It was announced today that the first patient in the TERRAIN study received their first dose in the Phase 2 trial of the investigational drug MDV3100 . MDV3100 is a triple-acting oral androgen receptor antagonist that I have writing about as a drug “On The Horizon”. Triple-acting means that it blocks testosterone binding to the androgen receptor, impedes movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation) and inhibits binding to DNA.
In the trial it is administered along with bicalutamide (generic casodex) since it seems to work in cells that have become resistant to bicalutamide, a commonly used anti-androgen, in the treatment of advanced prostate cancer patients who have progressed while on LHRH analogue therapy or following surgical castration (castrate resistant patients).
“MDV3100 has been shown in preclinical studies to provide more complete suppression of the androgen receptor pathway than existing anti-androgens and the TERRAIN study provides the opportunity to investigate this finding further in a clinical setting,” said Lynn Seely, M.D., chief medical officer of Medivation. “MDV3100 is currently in Phase 3 testing for advanced prostate cancer, but our goal is to determine if MDV3100 can benefit men with prostate cancer earlier in the course of the disease.”
The trial is expected to enroll approximately 370 patients in North America and Europe. The primary endpoint of the trial is progression-free survival. Information about patient eligibility and enrollment can be obtained by calling 800-888-7704 ext. 5473 or e-mailing firstname.lastname@example.org.
“This is the first of two Phase 2 trials in earlier-stage disease that we will initiate this year to evaluate the potential benefit of MDV3100 in a broad spectrum of prostate cancer patients,” said Steven Ryder, M.D., president, Astellas Pharma Global Development. “The second of our new Phase 2 trials will study MDV3100 in an even earlier-stage population — hormone naive prostate cancer patients who are indicated for androgen deprivation therapy. We expect to begin that trial in the first half of this year.”
In addition to the TERRAIN study, MDV3100 is currently being evaluated in two global Phase 3 studies in patients with advanced prostate cancer. The randomized, double-blind, placebo-controlled Phase 3 AFFIRM trial completed enrollment in November 2010. This trial of 1,199 patients with advanced prostate cancer who were previously treated with docetaxel-based chemotherapy is evaluating 160 mg/day of MDV3100 versus placebo. The primary endpoint is overall survival.
A second Phase 3 clinical trial of MDV3100 in advanced prostate cancer, the PREVAIL trial, is currently enrolling patients. This randomized, double-blind, placebo-controlled, multi-national trial of approximately 1,700 men with advanced prostate cancer who have not yet received chemotherapy is evaluating MDV3100 at a dose of 160 mg taken orally once daily plus standard of care versus placebo plus standard of care. The co-primary endpoints of the trial are overall survival and progression-free survival. Information about patient eligibility and enrollment can be obtained by calling the PREVAIL study hotline toll-free at 1-888-243-4363.
Although behind abiraterone in the timing of trials, MDV3100 remains an exceptionally strong candidate to show survival benefits. I am thrilled that they will be expanding their trials to include men who are earlier in the progression of their disease. Sadly, many of the other companies have not responded to this need and taken on this task. Hopefully, this will serve as a model and we will see increasing trials for men who are pre-chemotherapy.
MDV3100 is an investigational therapy in clinical development for advanced prostate cancer. In a Phase 1-2 trial in 140 men with advanced prostate cancer published in The Lancet, encouraging anti-tumor activity was noted with MDV3100 across endpoints. In preclinical experiments published in Science in April 2009, the triple-acting, oral androgen receptor antagonist provided more complete suppression of the androgen receptor pathway than bicalutamide (casodex), the most commonly used anti-androgen.
Joel T. Nowak, M.A., M.S.W.