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    DRUG:

    opevesostat (MK-5684)

    i
    Other names: MK-5684, ODM-208, ODM 208, ODM208, MK 5684, MK5684
    Company:
    Merck (MSD), Orion Corp
    Drug class:
    CYP11A1 inhibitor
    Related drugs:
    2ms
    A Drug-Drug Interaction Study of Carbamazepine and Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-012) (clinicaltrials.gov)
    P1, N=14, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    opevesostat (MK-5684)
    2ms
    A Study of the Absorption, Distribution, Metabolism, and Elimination of Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-008) (clinicaltrials.gov)
    P1, N=8, Completed, Merck Sharp & Dohme LLC | Recruiting --> Completed
    Trial completion
    |
    opevesostat (MK-5684)
    2ms
    A Drug-Drug Interaction Study of Carbamazepine and Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-012) (clinicaltrials.gov)
    P1, N=14, Not yet recruiting, Merck Sharp & Dohme LLC
    New P1 trial
    |
    opevesostat (MK-5684)
    2ms
    A Study of the Absorption, Distribution, Metabolism, and Elimination of Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-008) (clinicaltrials.gov)
    P1, N=8, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    opevesostat (MK-5684)
    3ms
    A Drug-Drug Interaction Study of Diltiazem and MK-5684 in Healthy Adult Male Participants (MK-5684-011) (clinicaltrials.gov)
    P1, N=12, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed
    Trial completion
    |
    prednisone • opevesostat (MK-5684)
    4ms
    A Study of the Absorption, Distribution, Metabolism, and Elimination of Opevesostat (MK-5684) in Healthy Adult Male Participants (MK-5684-008) (clinicaltrials.gov)
    P1, N=8, Not yet recruiting, Merck Sharp & Dohme LLC
    New P1 trial
    |
    opevesostat (MK-5684)
    4ms
    A Study of Opevesostat (MK-5684) in China Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (MK-5684-001) (clinicaltrials.gov)
    P1, N=14, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2027 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Sep 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    opevesostat (MK-5684)
    4ms
    A Drug-Drug Interaction Study of Diltiazem and MK-5684 in Healthy Adult Male Participants (MK-5684-011) (clinicaltrials.gov)
    P1, N=12, Active, not recruiting, Merck Sharp & Dohme LLC
    New P1 trial
    |
    prednisone • opevesostat (MK-5684)
    4ms
    A Study of Opevesostat (MK-5684) in China Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (MK-5684-001) (clinicaltrials.gov)
    P1, N=14, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    opevesostat (MK-5684)
    5ms
    Opevesostat (MK-5684/ODM-208), an oral CYP11A1 inhibitor, in metastatic castration-resistant prostate cancer (mCRPC): Updated CYPIDES phase II results (ESMO 2024)
    53.0% and 36.8% had previously received both abiraterone and enzalutamide, and 69.7% and 64.7% had received cabazitaxel in patients with and without AR-LBD mutation respectively. Administration of Opevesostat to heavily pre-treated mCRPC patients shows promising antitumor activity. PSA50 responses were most frequent among patients harbouring activating AR-LBD mutations.
    P2 data • Metastases
    |
    AR positive • AR mutation
    |
    Guardant360® CDx
    |
    Xtandi (enzalutamide) • abiraterone acetate • cabazitaxel • opevesostat (MK-5684)
    7ms
    Substudy 01A: Safety and Efficacy of Opevesostat (MK-5684)-Based Treatment Combinations or Opevesostat Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A) (clinicaltrials.gov)
    P1/2, N=220, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Lynparza (olaparib) • docetaxel • cabazitaxel • opevesostat (MK-5684)
    7ms
    A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005) (clinicaltrials.gov)
    P1, N=6, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    opevesostat (MK-5684)
    8ms
    A Study of MK-5684 in China Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (MK-5684-001) (clinicaltrials.gov)
    P1, N=14, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2026 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Apr 2026
    Trial completion date • Trial primary completion date • Metastases
    |
    opevesostat (MK-5684)
    8ms
    Substudy 01A: Safety and Efficacy of MK-5684-based Treatment Combinations or MK-5684 Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A) (clinicaltrials.gov)
    P1/2, N=220, Not yet recruiting, Merck Sharp & Dohme LLC
    New P1/2 trial • Metastases
    |
    Lynparza (olaparib) • docetaxel • cabazitaxel • opevesostat (MK-5684)
    8ms
    Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology. (PubMed, Curr Opin Oncol)
    Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.
    Journal
    |
    CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1)
    |
    opevesostat (MK-5684)
    10ms
    Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer. (PubMed, NEJM Evid)
    In the Original Article, "Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer", originally published December 26, 2023 (DOI: https://doi.org/10.1056/EVIDoa2300171), in the Abstract, under "Background", the sentence "ODM-208, a novel inhibitor of cytochrome P450 17A1 …" should have read "ODM-208, a novel inhibitor of cytochrome P450 11A1…" A corrected version of the article has been posted at evidence.nejm.org.
    Journal
    |
    CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1)
    |
    opevesostat (MK-5684)
    11ms
    CYPIDES: Safety and Pharmacokinetics of ODM-208 in Patients With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=204, Active, not recruiting, Orion Corporation, Orion Pharma | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    opevesostat (MK-5684) • midazolam hydrochloride
    11ms
    A Study of MK-5684 in China Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (MK-5684-001) (clinicaltrials.gov)
    P1, N=14, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    opevesostat (MK-5684)
    11ms
    Study of MK-5684 Versus Alternative NHA in mCRPC (MK-5684-003) (clinicaltrials.gov)
    P3, N=1200, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting | Trial completion date: Jun 2029 --> Aug 2028
    Enrollment open • Trial completion date • Metastases
    |
    AR mutation
    |
    Xtandi (enzalutamide) • abiraterone acetate • prednisone • dexamethasone • opevesostat (MK-5684) • Yonsa (abiraterone acetate)
    12ms
    A Study of MK-5684 Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004) (clinicaltrials.gov)
    P3, N=1500, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    Xtandi (enzalutamide) • abiraterone acetate • prednisone • dexamethasone • opevesostat (MK-5684) • Yonsa (abiraterone acetate)
    1year
    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. (ASCO-GU 2024)
    53% and 33.8% of patients had previously received both abiraterone and enzalutamide, and 63.6% and 55.9% patients had received cabazitaxel in AR-LBD mutation positive and negative groups respectively. Administration of MK-5684 to heavily pre-treated mCRPC patients showed promising antitumor activity. PSA50 responses were most frequent among patients harboring activating AR-LBD mutations. Clinical trial information: NCT03436485.
    P2 data • Clinical • Metastases
    |
    AR positive • AR mutation
    |
    Guardant360® CDx
    |
    Xtandi (enzalutamide) • abiraterone acetate • cabazitaxel • opevesostat (MK-5684)
    1year
    A Study of MK-5684 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005) (clinicaltrials.gov)
    P1, N=6, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    opevesostat (MK-5684)
    1year
    A Study of MK-5684 in China Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (MK-5684-001) (clinicaltrials.gov)
    P1, N=14, Not yet recruiting, Merck Sharp & Dohme LLC
    New P1 trial • Metastases
    |
    opevesostat (MK-5684)
    1year
    Study of MK-5684 Versus Alternative NHA in mCRPC (MK-5684-003) (clinicaltrials.gov)
    P3, N=1200, Not yet recruiting, Merck Sharp & Dohme LLC
    New P3 trial • Metastases
    |
    Xtandi (enzalutamide) • abiraterone acetate • prednisone • dexamethasone • opevesostat (MK-5684) • Yonsa (abiraterone acetate)
    1year
    A Study of MK-5684 Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004) (clinicaltrials.gov)
    P3, N=1500, Not yet recruiting, Merck Sharp & Dohme LLC
    New P3 trial • Metastases
    |
    Xtandi (enzalutamide) • abiraterone acetate • prednisone • dexamethasone • opevesostat (MK-5684) • Yonsa (abiraterone acetate)
    1year
    A Study of MK-5684 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005) (clinicaltrials.gov)
    P1, N=6, Not yet recruiting, Merck Sharp & Dohme LLC
    New P1 trial • Metastases
    |
    opevesostat (MK-5684)
    almost2years
    Androgen receptor (AR) mutations in men with metastatic castration-resistant prostate cancer (mCRPC): Incidence and natural history. (ASCO-GU 2023)
    Two early phase trials investigating CYP11A1 inhibitors - CYPIDES (ODM208, NCT03436485) and STESIDES (ODM209, NCT03878823) - recruited mCRPC patients with and without pre-specified AR LBD mutation...Overall, 212 (78%), 202 (74%), and 240 (88%) patients had received previous abiraterone, enzalutamide, and docetaxel respectively... AR LBD mutations were detected in ctDNA in 25% of men with advanced mCRPC treated with at least one ARSI. Their incidence was associated with a longer duration of treatment with enzalutamide and a longer time from CRPC and prostate cancer diagnosis. >
    Metastases
    |
    AR (Androgen receptor) • STING (stimulator of interferon response cGAMP interactor 1)
    |
    AR mutation • AR T878A • AR F877L • AR H875Y • AR L702H
    |
    Guardant360® CDx • FoundationOne® Liquid CDx
    |
    docetaxel • Xtandi (enzalutamide) • abiraterone acetate • opevesostat (MK-5684) • ODM-209
    over2years
    Preliminary phase II results of the CYPIDES study of ODM-208 in metastatic castration-resistant prostate (mCRPC) cancer patients (ESMO 2022)
    51% patients had previously received both abiraterone and enzalutamide, and 65% patients both docetaxel and cabazitaxel. Conclusions Administration of ODM-208 to heavily pre-treated mCRPC patients with AR LBD mutation was highly effective in blocking the production of steroid hormones and showed promising antitumor activity. NCT03436485.
    P2 data • Clinical
    |
    AR mutation
    |
    Guardant360® CDx
    |
    docetaxel • Xtandi (enzalutamide) • abiraterone acetate • cabazitaxel • opevesostat (MK-5684)