Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Abiraterone Acetate

Prednisone

Dexamethasone acetate

Fludrocortisone

Taxane

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

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.

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.

Opevesostat

Abiraterone acetate

Enzalutamide

Administered orally or IM as a rescue medication

Fludrocortisone acetate

Toll Free Number

Study Coordinator

Medical Director

This is a phase 3, randomized, open-label study of opevesostat compared to alternative abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer (mCRPC) with respect to overall survival (OS) and to radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria In Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) in participants with mCRPC previously treated with next-generation hormonal agent (NHA) and taxane-based chemotherapy. It is hypothesized that opevesostat is superior with respect to OS and rPFS per PCWG Modified RECIST 1.1 as assessed by BICR in androgen receptor ligand binding domain (AR LBD) mutation-negative and -positive participants.

Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)

A Phase 3 Randomized, Open-label Study of MK-5684 Versus Alternative Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Previously Treated With Next-generation Hormonal Agent (NHA) and Taxane-based Chemotherapy

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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 Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) or death due to any cause, whichever occurs first. rPFS in AR LBD mutation-positive 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 as assessed by BICR or death due to any cause, whichever occurs first. rPFS in AR LBD mutation-negative participants will be reported for each study arm.

TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first.

OR is determined by PCWG-modified RECIST 1.1 as assessed by BICR.

DOR is determined by PCWG-modified RECIST 1.1 as assessed by BICR.

TTPP is assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and opiate analgesic use (Analgesic Quantification Algorithm \[AQA\] Score).

The time from randomization to PSA progression. The PSA progression date is defined as the date of either: 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.

The time from randomization to the first occurrence of any of the following symptomatic skeletal-related events: 1) Use of EBRT to prevent or relieve skeletal symptoms; 2) new symptomatic pathologic bone fracture (vertebral or nonvertebral); 3) spinal cord compression; or 4) tumor-related orthopedic surgical 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.

Orion Corporation, Orion Pharma

Merck Sharp & Dohme LLC

BB 1101

Participants receive opevesostat 5 mg by oral tablets twice daily plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily continuously until progression. Hydrocortisone up to 100 mg oral dose will also be provided to participants for use as rescue medication.

Tablets to be taken orally as a recue medication.

The purpose of this study is to assess the efficacy and safety of opevesostat in the treatment of Japanese men with metastatic castration-resistant prostate cancer (mCRPC) previously treated with Next Generation Hormonal Agent (NHA) and taxane-based chemotherapy.

A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005)

A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of MK-5684 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)

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.

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 collected pre-dose and at multiple timepoints post-dose will be used to determine the Cmax.

Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Tmax.

Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-12.

Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Vz/F.

Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the CL/F.

Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the t½.

Percentage of participants in the analysis population who have a reduction in PSA level of ≥50% measured twice ≥3 weeks apart.

Time from first dose of study drug to PSA progression. PSA progression date is defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.

Time from first dose of study drug to radiographic progression, or death due to any cause, whichever occurs first.

Percentage of participants in the analysis population who have a best overall response of either confirmed Complete Response (CR) or a confirmed Partial Response (PR) per PCWG-modified RECIST 1.1.

Time from first documented evidence of confirmed Complete Response (CR) or Partial Response (PR) per PCWG-modified RECIST 1.1 until disease progression or death from any cause, whichever occurs first.

Time from first dose of study intervention to death due to any cause.

Blood samples collected at multiple timepoints after the administration of opevesostat will be used to determine the blood concentrations of steroids.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)	NCT06136624	Prostate Cancer...	Opevesostat Abiraterone ace... Enzalutamide Hydrocortisone Fludrocortisone... Prednisone Dexamethasone	-	Merck Sharp & Dohme LLC
A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005)	NCT06104449	Prostatic Neopl... Metastatic Cast...	Opevesostat Dexamethasone Fludrocortisone... Hydrocortisone	18 Years -	Merck Sharp & Dohme LLC
A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005)	NCT06104449	Prostatic Neopl... Metastatic Cast...	Opevesostat Dexamethasone Fludrocortisone... Hydrocortisone	18 Years -	Merck Sharp & Dohme LLC
Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)	NCT06136624	Prostate Cancer...	Opevesostat Abiraterone ace... Enzalutamide Hydrocortisone Fludrocortisone... Prednisone Dexamethasone	-	Merck Sharp & Dohme LLC

Spots Global Cancer Trial Database for fludrocortisone acetate