It was announced today that the phase I/II trial of MDV3100 demonstrated positive results. MDV3100 is a novel triple-acting oral androgen receptor antagonist, the common antagonist most of us are familiar with today is Casodex. These results were published in the online April 15 version of The Lancet.

The trial used MDV3100 in men with progressive, metastatic castration-resistant prostate cancer (mCRPC). According to the Lancet, MDV3100 demonstrated anti-tumor activity in men with late-stage prostate cancer. The evaluative criteria were reductions in prostate specific antigen (PSA) levels, radiographic findings and circulating tumor cell (CTC) counts. It was also reported that anti-tumor effects were observed in men who were resistant to standard anti-androgen treatments, as well as in men who had progressed following chemotherapy. MDV3100 is currently in Phase 3 trial development for the treatment of advanced prostate cancer.

According to Howard Scher, M.D., lead author of The Lancet article and chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center in New York, “MDV3100, with its unique mechanism of action, could offer an important new treatment option to men with prostate cancer that is resistant to currently available anti-androgens. It is particularly encouraging that antitumor activity was seen on all outcomes assessed in patients who had failed chemotherapy because their survival times are one year or less, on average, and their treatment options are limited.”

All of the men participating in the phase I/II trial had very progressed disease when they were enrolled. They were also very heavily pretreated, with 77 percent having failed at least two lines of prior hormonal therapy and 54 percent having failed one or more chemotherapy regimens. A total of 140 men were enrolled in the trial, which evaluated MDV3100 doses between 30 and 600 mg/day. During the trial the men were permitted to remain on treatment for as long as they continued to tolerate the drug and their disease did not progress. Efficacy endpoints included CTC counts, serum PSA levels, soft tissue and bony metastases, and time on treatment.

The Results of the Trial

MDV3100 was successfully associated with anti-tumor activity in men who were already resistant to bicalutamide (Casodex) as well as other standard anti-androgen treatments. This also included men who had failed prior chemotherapy (n=75) as well as those men who were chemotherapy-naïve (n=65). Anti-tumor activity was demonstrated by:
• Substantial reductions in PSA levels, including declines in serum PSA of 50 percent or more in 56 percent of patients.
o The PSA responses lasted for a median of 41 weeks for chemotherapy-naïve patients, 32 weeks for all patients and 21 weeks for post-chemotherapy patients.
• Improvement or stabilization in tumors that had spread to soft tissue or bone. Treatment with MDV3100 was associated with tumor regressions (22 percent of all patients — both chemotherapy-naïve and post-chemotherapy patients) and stable disease in soft tissue (49 percent of all patients) and stable disease in bone (56 percent of all patients).
o The median time to radiographic progression was not reached for chemotherapy- naïve patients; it was 47 weeks in all patients combined and 29 weeks for post-chemotherapy patients.
• A conversion from unfavorable to favorable CTCs in 49 percent of patients (75 percent of the chemotherapy-naïve and 37 percent of the post-chemotherapy groups). Of patients who initiated therapy with favorable counts, 91 percent retained favorable counts during treatment.

The morbidity problems were limited with most men able tolerate doses up to and including 240 mg/day. Fatigue was the most frequently reported adverse event. (Don’t forget the role of a phase I/II trial includes determining dosing levels).

“Based on the favorable benefit-risk ratio for MDV3100 observed in the Phase 1-2 trial, we initiated the randomized, placebo-controlled Phase 3 AFFIRM trial in men with progressive advanced prostate cancer following chemotherapy, as new treatments are urgently needed for this patient group,” said Lynn Seely, M.D., chief medical officer of Medivation. “We also plan to evaluate MDV3100 in earlier stages of prostate cancer, as those patients also are in need of new treatment options.”

Currently there is a phase III trial actively enrolling men in a clinical trial of MDV3100. This trial is designed for men with progressive disease following failed docetaxel treatment (chemotherapy). This phase III trial is known as AFFIRM, the randomized, placebo-controlled, double-blind, multi-national trial which is evaluating MDV3100 at a dose of 160 mg taken orally once daily in men with metastatic prostate cancer who were previously treated with docetaxel-based chemotherapy. The primary endpoint of the trial is overall survival; secondary endpoints include progression-free survival, safety and tolerability. The AFFIRM study is being conducted internationally with sites in Argentina, Austria, Australia, Belgium, Canada, Chile, France, Germany, Italy, Netherlands, Poland, South Africa, Spain, UK and U.S.

If you are interested in additional information about the trial, eligibility and enrollment you should go to: or call the AFFIRM study hot line, toll-free in the U.S. and Canada at 1-888-782-3256.

Information for this post was obtained from a press release from the pharmaceutical company.

Joel T Nowak, MA, MSW