Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Opevesostat, [¹⁴C]Opevesostat, ODM-208
MK-5684 · 9 trials · 12 indications
OS is defined as time from randomization to death due to any cause. OS in AR LBD mutation-positive participants will be reported for each study arm.
OS is defined as time from randomization to death due to any cause. OS in AR LBD mutation-negative participants will be reported for each study arm.
OS is defined as the time from randomization to death due to any cause.
For all cohorts, PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.
Blood samples will be collected to determine the AUC0-inf of MK-5684 in plasma.
Blood samples will be collected to determine the AUC0-last of MK-5684 in plasma.
Blood samples will be collected to determine the AUC0-24 of MK-5684 in plasma.
Blood samples will be collected to determine the Cmax of MK-5684 in plasma.
Blood samples will be collected to determine the Tmax of MK-5684 in plasma.
Blood samples will be collected to determine the t1/2 of MK-5684 in plasma.
Blood samples will be collected to determine the CL/F of MK-5684 in plasma.
Blood samples will be collected to determine the Vz/F of MK-5684 in plasma.
Urine samples will be collected at pre-specified timepoints and used to determine CumAeu.
Fecal samples will be collected at pre-specified timepoints and used to determine CumAef.
Urine samples will be collected at pre-specified timepoints and used to determine CumFeu.
Fecal samples will be collected at pre-specified timepoints and used to determine Cumfef.
Plasma samples will be collected at pre-specified timepoints and used to determine AUC0-t of opevesostat.
Plasma samples will be collected at pre-specified timepoints and used to determine AUC0-inf of opevesostat.
Plasma samples will be collected at pre-specified timepoints and used to determine Cmax of opevesostat.
Plasma samples will be collected at pre-specified timepoints and used to determine Tmax of opevesostat.
Plasma samples will be collected at pre-specified timepoints and used to determine t1/2 of opevesostat.
Plasma samples will be collected at pre-specified timepoints and used to determine AUC0-t of total radioactivity.
Plasma samples will be collected at pre-specified timepoints and used to determine AUC0-inf of total radioactivity.
Plasma samples will be collected at pre-specified timepoints and used to determine Cmax of total radioactivity.
Plasma samples will be collected at pre-specified timepoints and used to determine Tmax of total radioactivity.
Plasma samples will be collected at pre-specified timepoints and used to determine t1/2 of total radioactivity.
Plasma samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.
Urine samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.
Fecal samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.
AUC0-inf of MK-5684 in plasma will be determined.
AUC0-last of MK-5684 in plasma will be determined.
AUC0-24 of MK-5684 in plasma will be determined.
Cmax of MK-5684 in plasma will be determined.
Tmax of MK-5684 in plasma will be determined.
t1/2 of MK-5684 in plasma will be determined.
CL/F of MK-5684 in plasma will be determined.
Vz/F of MK-5684 in plasma will be determined.
The following events, if considered drug related by the investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not laboratory value); Grade 4 hematologic toxicity lasting \>7 days, except thrombocytopenia (Grade 4 thrombocytopenia of any duration, Grade 3 thrombocytopenia associated with clinically significant bleeding); Any nonhematologic adverse event (AE) \>Grade 3 in severity should be considered a DLT (with exceptions); Any Grade 3 or Grade 4 nonhematologic laboratory value (if certain criteria are met); Febrile neutropenia Grade 3 or Grade 4; Prolonged delay (\>2 weeks) in initiating treatment after the first 28 days due to study intervention-related toxicity; Missing \>25% of study intervention doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
The Prostate-specific Antigen (PSA) response rate is the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level will be confirmed by an additional PSA evaluation performed ≥3 weeks from the original response per Prostate Cancer Working Group (PCWG) criteria.
An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality.
Blood samples will be collected at pre-specified timepoints to determine the Cmax of opevesostat.
Blood samples will be collected at pre-specified timepoints to determine the Tmax of opevesostat.
Blood samples will be collected at pre-specified timepoints to determine the AUC0-12 of opevesostat.
Blood samples will be collected at pre-specified timepoints to determine the Vz/F of opevesostat.
Blood samples will be collected at pre-specified timepoints to determine the CL/F of opevesostat.
Blood samples will be collected at pre-specified timepoints to determine the t1/2 of opevesostat.
The following events, if considered drug related by the Investigator, will be considered a DLT: Grade 4 hematologic toxicity lasting ≥7 days, except anemia and thrombocytopenia; Grade 3 nausea, vomiting, diarrhea or fatigue lasting \>3 days despite optimal supportive care; other nonhematologic grade ≥3 toxicities of any duration (not laboratory); Grade ≥3 nonhematologic laboratory abnormality (if certain criteria are met); febrile neutropenia Grade 3 or Grade 4; missing \>25% of opevesostat doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity. The number of participants who experience a DLT will be presented.
| Arm | Type | Description |
|---|---|---|
| Opevesostat | EXPERIMENTAL | Participants receive opevesostat 5 mg by oral tablets twice daily (bid) plus dexamethasone 1.5 mg by oral tablets once daily (qd) and 0.1 mg fludrocortisone acetate by oral tablet qd until progression. Hydrocortisone 100 mg (oral or intramuscular \[IM\]) dose will also be provided to participants for use as rescue medication. Prior to study protocol amendment 9, prednisone was provided as a rescue medication during adrenal recovery, titrated at 5mg daily maintenance dose and then titrated to discontinuation. |
| Abiraterone Acetate or Enzalutamide | ACTIVE_COMPARATOR | Participants receive abiraterone 1000 mg qd by oral tablets plus prednisone 5 mg bid by oral tablets or enzalutamide 160 mg qd by oral tablets. |
| Daily Corticosteroids + Opevesostat | EXPERIMENTAL | Participants receive opevesostat 5 mg by oral tablets twice daily (BID) plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily (QD) continuously until disease progression. Hydrocortisone 100 mg (oral or intramuscular \[IM\]) will also be provided to participants for use as rescue medication. |
| Alternative Next-Generation Hormonal Agent (NHA) | ACTIVE_COMPARATOR | Participants receive abiraterone 1000mg QD by oral tablets plus prednisone 5 mg BID by oral tablets or enzalutamide 160 mg QD by oral tablets until disease progression. |
| MK-5684 and Daily Corticosteroids | EXPERIMENTAL | Participants with breast cancer, ovarian cancer, or endometrial cancer will receive 5 mg of MK-5684 orally twice daily. Participants will also receive fludrocortisone/fludrocortisone acetate starting at 0.1 mg orally, and dexamethasone/dexamethasone acetate starting at 1 mg orally; both will be adjusted individually during the study. Participants will receive treatment until one of the conditions for discontinuation of study intervention is met. |
| Fulvestrant or Exemestane | EXPERIMENTAL | Participants with breast cancer receive endocrine therapy of the physician's choice: either 500 mg of fulvestrant on Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter (cycles are 28 days in length) or 25 mg of exemestane once daily (QD). Participants will receive treatment until one of the conditions for discontinuation of study intervention is met. |
| Observation (No Treatment) | NO_INTERVENTION | Participants with ovarian cancer will be observed but will receive no treatment for the duration of the study. |
| Treatment of Physician's Choice | EXPERIMENTAL | Participants with endometrial cancer will receive the physician's choice of either 80 mg megestrol acetate/medroxyprogesterone acetate twice daily, or alternating between 80 mg megestrol acetate twice daily for three weeks and 20 mg tamoxifen twice daily for three weeks, or 2.5 mg letrozole once daily. Participants will receive treatment until one of the conditions for discontinuation of study intervention is met. |
| Group 1: Severe Renal Impairment (RI) | EXPERIMENTAL | Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal). |
| Group 2: End-stage renal disease (ESRD) | EXPERIMENTAL | Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) in Period 1 and Period 2. In Period 1, participants will receive a single oral dose of MK-5684 approximately 30 minutes prior to their normally scheduled hemodialysis (HD), followed by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing. In Period 2, participants will receive a single oral dose of MK-5684 immediately followed by completion of their normally scheduled HD, and by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing. |
| Group 3: Healthy Participants | EXPERIMENTAL | Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal). |
| [¹⁴C]Opevesostat | EXPERIMENTAL | On Day 1, participants receive a single dose of \[¹⁴C\]opevesostat as an oral solution. Participants then receive single doses of 5.0 mg prednisone and 0.05 mg fludrocortisone tablets 4 hours later as hormone replacement therapy. |
| MK-5684 Period 1 | EXPERIMENTAL | On Day 1 a single dose of MK-5684 will be administered under fasting conditions and a single dose of HRT (prednisone and fludrocortisone) will be administered under fed conditions approximately 4.5 hours after MK-5684 dosing. |
| MK-5684 Period 2 | EXPERIMENTAL | There will be a washout of at least 5 days between MK-5684 dosing in Period 1 and the first diltiazem dosing in Period 2. In Period 2, diltiazem will be administered once daily (QD) for 6 consecutive days with a single dose of MK-5684 coadministered on Day 2 under fasting conditions. HRT (prednisone and fludrocortisone) will be administered under fed conditions QD on Days 2 through 5, approximately 4.5 hours after MK-5684 and/or diltiazem dosing. |
| Arm A1: Opevesostat | EXPERIMENTAL | Participants receive 5 mg of opevesostat twice daily (BID) via oral tablet plus dexamethasone 1.5 mg by oral tablets once daily (QD) and 0.1 mg fludrocortisone acetate by oral tablet QD until progression or discontinuation. |
| Arm A2: Olaparib + Opevesostat | EXPERIMENTAL | Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 300 mg of olaparib BID via oral tablet until progressive disease or discontinuation. |
| Arm A3: Docetaxel + Opevesostat | EXPERIMENTAL | Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m\^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation. |
| Arm A4: Cabazitaxel + Opevesostat | EXPERIMENTAL | Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m\^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation. |
| Name | Type | Description |
|---|---|---|
| Opevesostat | DRUG | Administered orally |
| Abiraterone acetate | DRUG | Administered orally |
| Enzalutamide | DRUG | Administered orally |
| Hydrocortisone | DRUG | Administered orally or IM as a rescue medication |
| Fludrocortisone acetate | DRUG | Administered orally |
| Prednisone | DRUG | Administered orally as a rescue medication |
| Dexamethasone | DRUG | Administered orally as rescue medication |
| Prednisone acetate | DRUG | Administered orally |
| Fludrocortisone/ Fludrocortisone acetate | DRUG | Tablet for oral administration. |
| Dexamethasone/Dexamethasone acetate | DRUG | Tablet for oral administration. |
| Rescue Medications | DRUG | Hydrocortisone or hydrocortisone/hydrocortisone acetate administered via intramuscular injection as rescue medication. |
| Fulvestrant | DRUG | Administered via intramuscular injection. |
| Exemestane | DRUG | Tablet for oral administration. |
| Megestrol acetate/Medroxyprogesterone acetate | DRUG | Tablet for oral administration. |
| Tamoxifen | DRUG | Tablet for oral administration. |
| Letrozole | DRUG | Tablet for oral administration. |
| MK-5684 | DRUG | Oral tablet |
| [¹⁴C]Opevesostat | DRUG | Oral solution |
| Fludrocortisone | DRUG | Tablet |
| Diltiazem hydrocholoride | DRUG | Administered at a dose of 240 mg per dosing regimen via oral capsule (extended-release). |
| Olaparib | DRUG | Oral Tablet |
| Docetaxel | DRUG | IV Infusion |
| Cabazitaxel | DRUG | IV Infusion |
Inclusion Criteria: * Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology. * Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months before Screening * Has current evidence of distan...
MK-5684 is an investigational small molecule being developed by Merck & Company, Inc. (MRK). It is in Phase 1 clinical development and has been studied in trials involving chronic kidney failure and prostate cancer. It is not an approved medicine.
MK-5684 targets CYP11A1, an enzyme. By acting on this enzyme, the drug is designed to affect a specific step in hormone synthesis. This mechanism is the basis for its investigation in prostate cancer and related conditions.
MK-5684 is being developed by Merck & Company, Inc., which trades under the ticker MRK. The company is responsible for the clinical program, including the Phase 1 studies conducted in the United States.
MK-5684 is in Phase 1 clinical development. It is investigational and has not been approved by the FDA. The completed Phase 1 trials were designed to evaluate its effects in specific populations and drug interaction settings.
MK-5684 has been studied in two completed Phase 1 trials: NCT06814132, which evaluated its effect in male participants with severe renal impairment and end-stage renal disease, and NCT06554639, a drug-drug interaction study with diltiazem in healthy adult male participants.
MK-5684 is not approved for any use. It is being investigated in clinical trials for chronic kidney failure and prostate cancer. The completed Phase 1 studies assessed its profile in renal impairment and a drug interaction setting.