In an oral presentation at the ESMO Congress 2022, the lead author of the phase 2 CYPIDES trial, Karim Fizazi, discussed preliminary findings on ODM-208—a first-in-class CYP11A1 inhibitor—in the treatment of metastatic castration-resistant prostate cancer (mCRPC).
According to Fizazi, ODM-208 demonstrated “promising antitumor activity” in heavily pretreated patients with mCRPC with androgen receptor (AR) ligand binding domain (LBD) mutations. Additionally, ODM-208 was highly effective for blocking the production of steroid hormones that may activate the AR signaling pathway.
A total of 43 patients (median years of age, 68) with a prespecified AR LBD mutation were evaluable at the March 17, 2022, data cutoff. Participants received ODM-208 5 mg twice a day alongside dexamethasone and fludrocortisone. Efficacy was evaluated according to prostate-specific antigen (PSA) measures and RECIST response criteria.
Among the cohort, 51% of patients had previously received abiraterone and enzalutamide, and 65% had received docetaxel and cabazitaxel. Based on preliminary findings, Fizazi reported that ODM-208 induced a more than 50% best reduction in PSA in over half the participants, as well as at least 4 RECIST partial responses among 17 patients with matured data.
Additionally, Fizazi noted that ODM-208 had been well-tolerated and demonstrated a much lower rate of hospitalization for adrenal insufficiency to date when compared with the phase 1 study (2.3% vs 33%, respectively).
Overall, Fizazi and colleagues supported the potential value of ODM-208 for treating patients with mCRPC who are resistant to hormone-based therapies. The study is ongoing in 18 centers across France, Finland, the UK, and the US, and more mature data will be presented.