Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Conditions
Interventions
[Arm 1] I-DXd will be administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W).
[Arm 2] Docetaxel will be administered as an IV infusion on Day 1 of each cycle for up to 10 cyc
Sponsors
Fujita Tomoko
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology. - Has prostate cancer progression while on androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months prior to Screening. - Has progression under the following conditions if the participant received first generation antiandrogen therapy prior to enrollment: a. Evidence of progression >4 weeks since last flutamide treatment. b. Evidence of progression >6 weeks since last bicalutamide or nilutamide treatment. - Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by CT/MRI. - Has received prior treatment with 1 or 2 androgen receptor pathway inhibitor(s) for non-metastatic hormone-sensitive prostate cancer (nmHSPC), metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration resistant prostate cancer (nmCRPC), or mCRPC and progressed during or after at least 8 weeks of treatment. - Has ongoing androgen deprivation with serum testosterone =4 weeks prior to randomization. - Has had prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) if indicated by local approved regimen or were deemed ineligible to receive treatment by the investigator. - If capable of producing sperm, the participant agrees to continue contraception for during the intervention period and at least the time needed to eliminate each study intervention after the last dose of study intervention. - The participant has provided documented informed consent for the study. - Has provided tumor tissue from a core or excisional biopsy from soft tissue not previously irradiated and obtained after disease progression on the most recent prior therapy. - Participants who have adverse events (AE)s 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 (ART). - Participants who have adequate organ function. - 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 prior to randomization. - Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening. - An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 10 days before allocation/randomization.
Exclusion criteria
Exclusion criteria: - Has a gastrointestinal disorder affecting absorption. - Is unable to swallow tablets/capsules. - Clinically significant corneal disease. - History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids or has current ILD/pneumonitis and/or suspected ILD/pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening. - Has a clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses. - History of hypersensitivity, intolerance, or contraindications to taxanes, prednisone/prednisone acetate/prednisolone/prednisolone acetate, or any of the investigational drug substances, inactive ingredients in the drug product, or severe hypersensitivity reactions to other monoclonal antibodies. - Has Common Terminology Criteria for Adverse Events (CTCAE) V5.0 Grade >=3 peripheral neuropathy. - Has uncontrolled or significant cardiovascular disease. - Has received prior treatment with a taxane-based chemotherapy agent for mCRPC. - Has received prior treatment with orlotamab, enoblituzumab, or other B7-H3-targeted agents, including I-DXd. - Prior discontinuation of an antibody drug conjugate (ADC) that consists of an exatecan derivative due to treatment-related toxicities. - Chronic steroid treatment (dose of more than 10 mg daily prednisone equivalent). - Has received a whole blood transfusion in the last 120 days prior to entry into the study. - Has received colony-stimulating factors within 2 weeks prior to the first dose of study intervention. - Participant is currently receiving strong inhibitors of cytochrome P450 (CYP) 3A4 that cannot be discontinued for the duration of the study. - Inadequate treatment washout period before randomization/enrollment. - Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids. - 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 a "superscan" bone scan. - 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. - History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator. - History of allogeneic tissue/solid organ transplant. - Participants who have not adequately recovered from major surgery or have ongoing surgical complications. - Participants who are incapacitated are not eligible for this study. - Has undergone major surgery within 28 days before the date of randomization, and has not recovered from the toxicities and/or complications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Overall survival (OS) - Radiographic progression-free survival (rPFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| - Time to initiation of the first subsequent anticancer therapy (TFST) - Objective response (OR) and duration of response (DOR) - Time to pain progression (TTPP) - Time to prostate-specific antigen (PSA) progression - PSA response rate - Time to first symptomatic skeletal-related event (SSRE) - Safety and tolerability | — |
Countries
Argentina, Australia, Austria, Brazil, Chile, China, Colombia, Czech Republic, Denmark, France, Germany, Greece, Guatemala, Hong Kong, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Norway, Peru, Poland, Refer to 7-5, South Africa, South Korea, Spain, Sweden, Switzerland, Turkiye, United Kingdom
Contacts
Public ContactMSDJRCT inquiry mailbox
MSD K.K.
Outcome results
None listed