Reportedly, MDV3100 demonstrated anti-tumor activity in patients with late-stage prostate cancer as evaluated by reductions in prostate specific antigen (PSA) levels, radiographic findings and circulating tumor cell (CTC) counts.
The anti-tumor effects were observed in patients who were resistant to standard anti-androgen treatments, as well as in patients who had progressed following chemotherapy. MDV3100 is currently in Phase 3 development for the treatment of advanced prostate cancer.
In the trial, all patients in the open-label, dose-escalation, US Phase 1-2 clinical trial had progressive disease upon enrollment and were heavily pretreated, with 77% having failed at least two lines of prior hormonal therapy and 54% having failed one or more chemotherapy regimens.
A total of 140 men were enrolled in the trial, which evaluated MDV3100 doses between 30 and 600mg/day. Patients could 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.
Results showed that MDV3100 was associated with anti-tumor activity across a variety of endpoints in patients who had become resistant to bicalutamide (Casodex)1 or other standard anti-androgen treatments, including patients who had failed prior chemotherapy (n=75) and those who were chemotherapy-naive (n=65).
MDV3100 was generally well tolerated in the trial at doses up to and including 240mg/day.
Currently, both parties are enrolling patients in a Phase 3 clinical trial of MDV3100 in men with progressive disease following docetaxel treatment. Known as Affirm, the randomised, placebo-controlled, double-blind, multi-national trial is evaluating MDV3100 at a dose of 160mg 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.
Lynn Seely, chief medical officer of Medivation, said: “Based on the favorable benefit-risk ratio for MDV3100 observed in the Phase 1-2 trial, we initiated the randomised, 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. We also plan to evaluate MDV3100 in earlier stages of prostate cancer, as those patients also are in need of new treatment options.”