A Phase 3, Randomized, Open-label Study of MK-5684 (004) Versus Alternative Abiraterone Acetate or Enzalutamide in Participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) That Progressed On or After Prior Treatment with One Nextgeneration Hormonal Agent (NHA)
Primary:
Objective: To compare MK-5684 to alternative abiraterone acetate or enzalutamide with respect to rPFS per PCWG Modified RECIST 1.1, as assessed by BICR in participants with mCRPC
Hypothesis (H1): MK-5684 is superior to alternative abiraterone acetate or enzalutamide with respect to rPFS per PCWG Modified RECIST 1.1 as assessed by BICR in AR LBD mutation positive participants.
Hypothesis (H3): MK-5684 is superior to alternative abiraterone acetate or
enzalutamide with respect to rPFS per PCWG Modified RECIST 1.1 as assessed by BICR in AR LBD mutation negative participants.
To compare MK-5684 to alternative abiraterone acetate or enzalutamide with respect to overall survival in participants with mCRPC.
Hypothesis (H2): MK-5684 is superior to alternative abiraterone acetate or enzalutamide with respect to overall survival in AR LBD mutation positive
participants.
Hypothesis (H4): MK-5684 is superior to alternative abiraterone acetate or enzalutamide with respect to overall survival in AR LBD mutation negative
participants.
Abiraterone
Enzalutamide
MK-5684
- Rutgers Cancer Institute of New Jersey
- Rutgers Cancer Institute of New Jersey-University Hospital
Inclusion Criteria
The main inclusion criteria include but are not limited to the following:
- Have histologically or cytologically confirmed adenocarcinoma of the prostate
without small cell histology
- Has current evidence of metastatic disease documented by either bone lesions on bone
scan and/or soft tissue disease shown by computed tomography scan (CT)/magnetic
resonance imaging (MRI)
- Has prostate cancer progression while receiving androgen deprivation therapy (ADT)
(or post bilateral orchiectomy) within 6 months before screening
- Has disease that progressed during or after treatment with one next-generation
hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) metastatic hormone
sensitive prostate cancer (mHSPC) or non metastatic hormone sensitive prostate
cancer (nmHSPC), for at least 8 weeks (at least 14 weeks for participants with bone
progression) Note: Participants may have received abiraterone acetate and docetaxel
or darolutamide and docetaxel for HSPC. However, participants must have received no
more than six cycles of docetaxel and had no radiographic disease progression while
receiving docetaxel
- Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed
within 7 days before randomization
- Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)
- Has had prior treatment with Poly polymerase inhibitors (PARPi) or were deemed
ineligible to receive treatment by the investigator or have refused PARPi treatment
- Has adequate organ function
- Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue
not previously irradiated. Samples from tumors progressing at a prior site of
radiation are allowed
- 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 before randomization
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
viral load is undetectable at Screening
- Participants who have adverse event (AEs) due to previous anticancer therapies must
have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who
are adequately treated with hormone replacement therapy (HRT) or participants who
have ≤Grade 2 neuropathy are eligible
- Human immunodeficiency virus (HIV)-infected participants must have well controlled
HIV on antiretroviral therapy (ART)
Exclusion Criteria
The main exclusion criteria include but are not limited to the following:
- Has presence of gastrointestinal condition
- Is unable to swallow capsules/tablets
- Has history of pituitary dysfunction
- Has poorly controlled diabetes mellitus
- Has a history of active or unstable cardio/cerebro-vascular disease, including
thromboembolic events
- Has clinically significant abnormal serum potassium or sodium level
- Has any of the following at screening visit: Hypotension: systolic blood pressure
(BP) <110 mmHg, or Uncontrolled hypertension: systolic BP >160mmHg or diastolic
blood BP >90 mmHg, in 2 out of the 3 recordings with optimized antihypertensive
therapy
- History or family history of long QTc syndrome
- Has a history of seizure(s) within 6 months prior to signing the informed consent
(IC) or has any condition that may predispose to seizure within 12 months prior to
the date of enrollment
- Has a history of clinically significant ventricular arrhythmias or Mobitz II second
degree or third-degree heart block without a permanent pacemaker in place
- Has received a taxane-based chemotherapy and or NHA for metastatic
castration-resistant prostate cancer (mCRPC)
- Has not adequately recovered from major surgery or have ongoing surgical
complications
- Has received prior treatment with radium for prostate cancer
- Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic
drugs for seizures
- Participants on an unstable dose of thyroid hormone therapy within 6 months before
the start of the study intervention
- Receives prior radiotherapy within 2 weeks before the first dose of study
intervention, or radiation-related toxicities, requiring corticosteroids
- Receives prior systemic anticancer therapy including investigational agents within 4
weeks before the first dose of study intervention
- Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein
(P-gp) inhibitors within 2 weeks before the first dose of study intervention
- Has received prior targeted small molecule therapy or NHA treatment within 4 weeks
before the first dose of study intervention
- Received a live or live-attenuated vaccine within 30 days before the first dose of
study intervention
- Has received an investigational agent or has used an investigational device within 4
weeks prior to study intervention administration
- Has known hypersensitivity to the components or excipients in abiraterone acetate,
prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or
opevesostat.
- Has a "superscan" bone scan defined as an intense symmetric activity in the bones
and diminished renal parenchymal activity on baseline bone scan such that the
presence of additional metastases in the future could not be evaluated
- Has known additional malignancy that is progressing or has required active treatment
within the past 3 years
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study medication
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Participants with previously treated brain metastases may participate
provided they are radiologically stable, (ie, without evidence of progression) for
at least 4 weeks as confirmed by repeat imaging performed during study screening,
are clinically stable and have not required steroid treatment for at least 14 days
prior to the first dose of study intervention
- Has active autoimmune disease that has required systemic treatment in the past 2
years. Replacement therapy is allowed
- Active infection requiring systemic therapy
- Has concurrent active Hepatitis B virus and Hepatitis C virus infection
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
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