Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Opevesostat · 10 trials · 10 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.
rPFS is defined as the time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 by BICR or death due to any cause, whichever occurs first.
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 opevesostat.
Blood samples will be collected to determine the AUC0-last of opevesostat.
Blood samples will be collected to determine the Cmax of opevesostat.
Blood samples will be collected to determine the Tmax of opevesostat.
Blood samples will be collected to determine the t1/2 of opevesostat.
Blood samples will be collected to determine the CL/F of opevesostat.
Blood samples will be collected to determine the Vz/F of opevesostat.
Plasma samples will be collected to determine the AUC0-inf of opevesostat.
Plasma samples will be collected to determine the AUC0-last of opevesostat.
Plasma samples will be collected to determine the AUC0-24 of opevesostat.
Plasma samples will be collected to determine the Cmax of opevesostat.
Plasma samples will be collected to determine the Tmax of opevesostat.
Plasma samples will be collected to determine the t1/2 of opevesostat.
Plasma samples will be collected to determine the CL/F of opevesostat.
Plasma samples will be collected to determine the Vz/F of opevesostat.
AUC0-inf of opevesostat in plasma will be determined.
AUC0-last of opevesostat in plasma will be determined.
AUC0-24 of opevesostat in plasma will be determined.
Cmax of opevesostat in plasma will be determined.
Tmax of opevesostat in plasma will be determined.
t1/2 of opevesostat in plasma will be determined.
CL/F of opevesostat in plasma will be determined.
Vz/F of opevesostat in plasma will be determined.
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.
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. |
| Opevesostat Period 1 | EXPERIMENTAL | On Day 1, a single dose of opevesostat will be administered under fed conditions. A single dose of steroid replacement (prednisone and fludrocortisone) will be administered under fed conditions approximately 4.5 hours after opevesostat dosing. |
| Opevesostat Period 2 | EXPERIMENTAL | There will be a washout of at least 5 days between opevesostat dosing in Period 1 and the first itraconazole dosing in Period 2. In Period 2, itraconazole will be administered once daily (QD) for 9 consecutive days with a single dose of opevesostat coadministered on Day 4 under fed conditions. Steroid replacement (prednisone and fludrocortisone) will be administered under fed conditions QD on Days 4 through 6, approximately 4.5 hours after opevesostat and/or itraconazole dosing. |
| Moderate Hepatic Impairment | EXPERIMENTAL | On Day 1, participants with moderate hepatic impairment will receive a single oral dose of opevesostat under fasting conditions and a single dose of hormone replacement therapy (HRT) (prednisone and fludrocortisone acetate) under fed conditions approximately 4.5 hours after opevesostat dosing. Participants with moderate hepatic impairment will receive another dose of HRT on Day 2. |
| Healthy | EXPERIMENTAL | On Day 1, healthy participants will receive a single oral dose of opevesostat under fasting conditions and a single dose of HRT (prednisone and fludrocortisone acetate) under fed conditions approximately 4.5 hours after opevesostat dosing. |
| [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. |
| 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. |
| Itraconazole | DRUG | Administered via oral capsule |
| Carbamazepine | DRUG | Administered at a dose of 100 mg, 200 mg, or 300 mg BID dependent on dosing regimen via oral capsule (extended-release). |
| [¹⁴C]Opevesostat | DRUG | Oral solution |
| Fludrocortisone | DRUG | Tablet |
| 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...
Opevesostat is an investigational small molecule being studied for the treatment of prostate cancer, including metastatic castration-resistant prostate cancer (mCRPC) and other prostatic neoplasms. It is being evaluated in clinical trials for patients with metastatic prostate cancer and castration-resistant disease.
Opevesostat is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with prostate cancer.
Opevesostat is in Phase 1 clinical development for prostate cancer indications. It has completed Phase 1 studies in Japanese and Chinese participants with metastatic castration-resistant prostate cancer, and an additional Phase 1 study in participants with hepatic impairment has also been completed.
Opevesostat has been studied in several clinical trials, including NCT06104449 in Japanese participants and NCT06136598 in Chinese participants with metastatic castration-resistant prostate cancer, both Phase 1 and completed. A Phase 3 trial, NCT06136650, is recruiting participants with mCRPC post one next-generation hormonal agent.
Yes, Opevesostat is also known as MK-5684. Clinical trial titles reference both names, such as 'A Study of Opevesostat (MK-5684) in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)'.
Opevesostat is a small molecule that belongs to the -stat class of enzyme inhibitors. It is being investigated for its ability to target enzymes involved in prostate cancer progression, though the specific molecular target has not been disclosed in the available trial information.