Merck & Orion Launch Phase 3 Trials in China for First-in-Class Oral CYP11A1 Inhibitor MK-5684 in Metastatic Castration-Resistant Prostate Cancer

Screenshot source:China Drug Clinical Trial Registration and Information Disclosure Platform

Prostate cancer is one of the common cancers in men.The growth of prostate cancer cells is androgen-dependent, so patients are initially sensitive to androgen deprivation therapy (ADT), whilePatients who experience disease progression after continuous ADT will develop intoMetastatic Castration-Resistant Prostate Cancer (mCRPC),Such patientsThe tumor has spread beyond the prostate.Research shows,Steroid hormones are one of the key factors driving prostate cancer.FineCytochrome P450 11A1 (CYP11A1）Is an important rate-limiting enzyme in the process of steroid synthesis,Targeting CYP11A1 provides an effective means of inhibiting steroid hormone production.

MK-5684 (also known asODM-208) is a potential "first-in-class" drug discovered and developed by Orion Corporation.CYP11A1-Specific Oral Non-Steroidal Inhibitor, developed for the treatment ofProstate cancer, etc.Hormone-dependent cancers. By inhibiting the activity of the CYP11A1 enzyme,MK-5684Can inhibit the production of all steroid hormones and hormone precursors that may activate the androgen receptor (AR) signaling pathway.This is particularly relevant for patients with somatic point mutations that activate the AR ligand-binding domain (LBD), which is one of the mechanisms of resistance to hormone therapy in mCRPC.

In July 2022, MSD announced a global R&D collaboration with Orion Corporation.Agreement, to jointly develop the latter's investigational therapy ODM-208 and other drugs targeting CYP11A1. Both partiesWill jointly develop and commercialize ODM-208,Orion Corporation will receive an upfront payment of $290 million.

This timeMSD and Orion CorporationThe two clinical studies launched in China are: oneRandomized, Open-label,Phase 3Research, AimInmCRPC with disease progression during or after prior treatment with one novel hormonal agent (NHA)PatientCompare the efficacy of MK-5684 with optional abiraterone acetate or enzalutamide in China; another one isRandomized, Open-labelPhase 3Research, AimInmCRPC patients previously treated with NHA and taxane-based chemotherapyCompare the efficacy of MK-5684 with optional abiraterone acetate or enzalutamide in China.

According to the publication in January 2024InData from the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU),MK-5684 inWith or withoutAR-LBDMutatedmCRPC PatientsPhase 2 clinical study achieves positive results. A total of 66 cases were included in the study.AR-LBDMutation-positive and 68 casesAR-LBDAmong mutation-negative patients, 53% and 33.8% of patients in the two groups had receivedAcetic Acid ABitelon orEnzalutamideTreatment, 63.6% and 55.9% of patients had received cabazitaxel. The results showed that MK-5684 could profoundly inhibit androgen synthesis, leading toAR-LBDMutation and No MutationAR-LBDAmong the patients with mutations, respectively55.6% and 16.7%Patients with PSA50 (Prostate-Specific AntigenPSAReduced by ≥50%)Response: 69.8% and 30.0% of patients achieved a PSA30 response.。MK-5684 was well-tolerated, with the most common treatment-related adverse events associated with adrenal suppression.

[2]MK-5684 (ODM-208), a CYP11A1 inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) with and without AR-LBD mutations: CYPIDES phase 2 results. Retrieved Jan 29，2024, From https://ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.159