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)

Prostatic Neoplasms, Castration-Resistant Clinical Trial

Official title:

MK-5684-01A Substudy: A Phase 1/2 Umbrella Substudy of MK-5684-U01 Master Protocol to Evaluate the Safety and Efficacy of MK-5684-based Treatment Combinations or MK-5684 Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06353386
• Other study ID #: 5684-01A
• Secondary ID: MK-5684-01A2023-
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 20, 2024
• Est. completion date: March 31, 2028

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Substudy 01A is part of a larger research study that is testing experimental treatments for metastatic castration-resistant prostate cancer (mCRPC). The larger study is the umbrella study (U01).

The goal of substudy 01A is to evaluate the safety and efficacy of opevesostat-based treatment combinations, or as a single agent, in participants with mCRPC.

This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for the opevesostat-based treatment combinations. There will be no hypothesis testing in this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: March 31, 2028
• Est. primary completion date: March 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without small cell histology.

• Prostate cancer progression and received androgen deprivation therapy (ADT) or post bilateral orchiectomy within 6 months before screening.

• Evidence of disease progression from either, >4 weeks from last flutamide treatment, or >6 weeks from last bicalutamide or nilutamide treatment, if receiving first generation anti-androgen therapy as last treatment therapy.

• Current evidence of metastatic disease.

• Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, or metastatic, hormone-sensitive prostate cancer or castration-resistant prostate cancer and have disease progression during or after treatment.

• Treatment with bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for >4 weeks before randomization.

• Participants who experienced adverse events (AEs) due to previous anticancer therapies must have recovered to <Grade 1 or baseline.

• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.

• Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load.

• Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• History of pituitary dysfunction.

• Poorly controlled diabetes mellitus.

• Active or unstable cardio/cerebro-vascular disease, including thromboembolic events.

• History or family history of long corrected QT interval (QTc) syndrome.

• Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestive of MDS/AML.

• History or current condition of adrenal insufficiency.

• History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.

• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.

• Undergone major surgery, including local prostate intervention (except prostate biopsy) within 28 days before randomization, and has not recovered from the toxicities and/or complications.

• Is on an unstable dose of thyroid hormone therapy within 6 months prior to first dose of study intervention.

• Received a whole blood transfusion in the last 120 days before randomization (packed red blood cells and platelet transfusions are acceptable if not given within 28 days before randomization).

• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.

• Received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities, requiring corticosteroids.

• Received a live or live-attenuated vaccine within 30 days before the first does of study intervention. Administration of killed vaccines is allowed.

• Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, or any other form of immunosuppressive therapy, within 7 days prior to the first dose of study intervention.

• Known additional malignancy that is progressing or has required active treatment within the past 3 years.

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Active autoimmune disease that has required systemic treatment in the past 2 years.

• Active infection requiring systemic therapy.

• Concurrent active HBV and HCV infections.

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant

Intervention

Drug:
• Opevesostat
Oral Tablet
• Olaparib
Oral Tablet
• Docetaxel
IV Infusion
• Cabazitaxel
IV Infusion
• Fludrocortisone acetate
Oral Tablet
• Dexamethasone
Oral Tablet
• Prednisone
Oral Tablet

Locations

Country	Name	City	State
Australia	Gallipoli Medical Research Ltd-GMRF CTU ( Site 0107)	Greenslopes	Queensland
Australia	Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110)	Melbourne	Victoria
Israel	Rambam Health Care Campus-Oncology Division ( Site 1002)	Haifa
Israel	Rabin Medical Center ( Site 1001)	Petah Tikva
Israel	Sheba Medical Center ( Site 1000)	Ramat Gan
Korea, Republic of	Samsung Medical Center-Division of Hematology/Oncology ( Site 1501)	Seoul
Taiwan	China Medical University Hospital ( Site 1703)	Taichung

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Orion Corporation, Orion Pharma

Countries where clinical trial is conducted

Australia,  Israel,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants who experience one or more dose-limiting toxicities (DLTs)	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.	Up to approximately 28 days
Primary	Number of participants who experience one or more adverse events (AEs)	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.	Up to approximately 46 months
Primary	Number of participants who discontinue study intervention due to an AE	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.	Up to approximately 46 months
Primary	Prostate-specific antigen (PSA) response rate	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.	Up to approximately 46 months
Secondary	Objective response rate (ORR)	The ORR is defined as the percentage of participants with complete response (CR: disappearance of all target lesions per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1); and no evidence of disease (NED) on base scan per Prostate Cancer Working Group (PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG). ORR will be assessed by Blinded Independent Central Review (BICR).	Up to approximately 46 months
Secondary	Radiographic progression-free survival (rPFS)	rPFS is defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 is =20% increase in the sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria is the appearance of =2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and are persistent for =6 weeks. rPFS will be assessed by BICR.	Up to approximately 46 months
Secondary	Overall survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 46 months
Secondary	Duration of response (DOR)	DOR is defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 is defined as at least a 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 a least 5 mm. PD per PCWG is the appearance of >2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and are persistent for >6 weeks. DOR will be assessed by BICR.	Up to approximately 46 months
Secondary	Time to first subsequent anticancer therapy (TFST)	TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first.	Up to approximately 46 months
Secondary	Time to pain progression (TTPP)	TTPP is defined as the time from randomization to pain progression based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 "worst pain in 24 hours" and by opiate analgesic use.	Up to approximately 46 months

External Links

•   Merck Clinical Trials Information
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