Phase 1 study of MK-5684 in Japanese Participants with mCRPC

JRCT ID: jRCT2031230431

Registered date:04/11/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Metastatic Castration-resistant Prostate Cancer
• Date of first enrollment: 14/11/2023
• Target sample size: 8
• Study type: Interventional
• Intervention(s): Participants will receive MK-5684 5 mg PO BID with hormone replacement therapy of 1.5 mg dexamethasone PO once daily (QD) and 0.1 mg fludrocortisone acetate PO QD until documented disease progression, unacceptable AEs, or any other discontinuation criteria is met.

Outcome(s)

Primary Outcome

- Dose limiting toxicities
- Adverse events(AEs)
- Study intervention discontinuation due to an AE

Secondary Outcome

- Plasma concentration of MK-5684 and derived PK parameters
- Prostate specific antigen (PSA)
- Time to PSA progression
- Radiographic progression-free survival (rPFS)
- Objective Response (OR)
- Duration of response (DOR)
- Overall survival (OS)
- Blood concentrations of steroids

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Male

Include criteria

- Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology and Have received, or been intolerant to, all treatment known to confer clinical benefit.
- Have current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by CT/MRI.
- Have ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nmol/L).
- Participants receiving bone anti-resorptive therapy must have been on stable doses for >=4 weeks prior to the start of study intervention.
- Have progressed on or after treatment with at least 1 line of next generation hormonal agents (NHAs) in metastatic hormone-sensitive prostate cancer (mHSPC) or in CRPC for a minimum of 12 weeks (e.g. abiraterone, enzalutamide, darolutamide, apalutamide), and with at least 1 line of taxane-based chemotherapy in mHSPC or in CRPC, or ineligibility for chemotherapy.
- Have prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening, as determined by the investigator through one of the following:
- PSA progression
- Radiographic disease progression in soft tissue based on RECIST 1.1, with or without PSA progression
- Radiographic disease progression in bone per Prostate Cancer Working Group (PCWG) 3
- Have a performance status of 0 or 1 on the ECOG Performance Scale
- Have a life expectancy of at least 3 months, based on the investigator assessment.
- Have adequate organ function
- A male participant is eligible to participate if he agrees to use contraception during the intervention period and for at least 7 days after the last dose of MK-5684.
- Participants who have AEs due to previous anticancer therapies must have recovered to <=Grade 1 or baseline.

Exclude criteria

- Has a history of pituitary dysfunction.
- Has brain metastases.
- History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
- Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
- Has an active infection or other medical condition that would make corticosteroid contraindicated.
- Has serious persistent infection within 2 weeks prior to the start of the study intervention.
- Participants on an unstable dose of thyroid hormone therapy within 6 months prior to the start of the study intervention.
- Has poorly controlled diabetes mellitus.
- Hypotension or uncontrolled hypertension.
- Has clinically significant abnormal serum potassium or sodium level.
- Has active or unstable cardio/cerebro-vascular disease, including thromboembolic events.
- Is unable to swallow orally administered medication or known gastrointestinal (GI) disease or GI procedure that may interfere with absorption of study intervention.
- Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to the start of the study intervention and not adequately recovered from the toxicities and/or complications.
- Has received aldosterone antagonist and phenytoin within 4 weeks prior to the start of the study intervention.
- Has received radiotherapy within 4 weeks prior to the start of the study intervention, or radiation related toxicities, requiring corticosteroids.
- Has received chemotherapy within the last 4 weeks prior to the start of the study intervention.
- Has received prior enzalutamide and apalutamide within 3 weeks, or abiraterone and darolutamide within 2 weeks prior to the start of the study intervention.
- Has received other anticancer therapy (excluding LHRH agonists or antagonists) within 4 weeks prior to the start of the study intervention, or immune checkpoint inhibitor within 12 weeks prior to the start of the study intervention.

Related Information

• Primary Sponsor: Koh Yasuhiro
• Secondary ID(s): NCT06104449