The goal of this clinical trial is to learn if tinengotinib combined with darolutamide or enzalutamide works to treat participants with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior androgen receptor pathway inhibitors (ARPIs). It will also learn about the safety of the combination therapy. The main questions it aims to answer are:
1. If participants with mCRPC can benefit from the combination therapy of tinengotinib plus one ARPI? 2. What medical problems do participants have when taking the combination therapy? Participants will take tinengotinib with darolutamide or enzalutamide to find the optimal dose and regimen of tinengotinib for the combination therapy in stage A. In stage B, participants will take preferred combination regimen of tinengotinib plus darolutamide/enzalutamide identified in stage A. In stage C, researchers will compare selected combination therapy versus standard treatment and/or monotherapy to see if the combination therapy works better.
Male aged >= 18 years at the time of signing the informed consent form (ICF).
Histologically or cytologically confirmed prostate adenocarcinoma; neuroendocrine differentiation after prior treatment is permitted (patients with de novo neuroendocrine prostate cancer at initial diagnosis are excluded).
Baseline imaging confirming metastatic lesions in bone (>=2 bone lesions) or soft tissue; lesions identified only by PET imaging are not acceptable.
Receipt of continuous medical castration for >=90 days or prior surgical castration, with serum testosterone < 50 ng/dL (1.73 nmol/L) within 28 days prior to the first dose. Participants receiving medical castration with a luteinizing hormone-releasing hormone (LHRH) analogue must continue treatment throughout the study.
Prior treatment with tyrosine kinase inhibitors (TKIs).
Prior treatment with darolutamide or enzalutamide (except for treatment duration <= 1 month).
Uncontrolled hypertension (systolic blood pressure >=150 mmHg or diastolic blood pressure >=100 mmHg; repeat measurement is permitted after an interval of >=10 minutes if abnormal), or a medical history of hypertensive crisis/hypertensive encephalopathy. Uncontrolled is defined as failure to achieve blood pressure control despite antihypertensive therapy with stable type/dose for at least 1 week.
Concurrent central nervous system (CNS) metastases with radiological or symptomatic progression within 28 days prior to study treatment initiation.
Parallel
tinengotinib 10 mg QD plus darolutamide
DrugParticipants will receive tinengotinib 10 mg once daily with darolutamide in 21-day cycles per protocol defined schedule.
tinengotinib 10 mg QD (2-week on / 1-week off) plus darolutamide
DrugParticipants will receive tinengotinib 10 mg once daily (2-week on / 1-week off) with darolutamide in 21-day cycles per protocol defined schedule.
tinengotinib 10 mg QD plus enzalutamide
DrugParticipants will receive tinengotinib 10 mg once daily with enzalutamide in 21-day cycles per protocol defined schedule.
preferred combination regimen of tinengotinib plus one ARPI
DrugParticipants will receive preferred combination regimen of tinengotinib at optimized dose plus one ARPI in 21-day cycles per protocol defined schedule.
selected combination regimen of tinengotinib plus one ARPI
DrugParticipants will receive selected combination regimen of tinengotinib at optimized dose plus one ARPI in 21-day cycles per protocol defined schedule.
Darolutamide 600 mg twice daily
DrugParticipants will receive darolutamide 600 mg twice daily in 21-day cycles per protocol defined schedule.
Enzalutamide 160mg daily (oral)
DrugParticipants will receive enzalutamide 160mg daily (oral) in 21-day cycles per protocol defined schedule.
7
Treatment groupsSee each treatment group below.
Stage A: safety evaluation parameters
Including dose-limiting toxicities (DLTs), and incidence, duration, and severity of other adverse events (AEs)
Stage B: 6-month PFS rate (6mo-PFS)
The proportion of patients who remain alive without disease progression at 6 months after study treatment initiation. Tumor assessments are based on RECIST v1.1 and/or PCWG3.
Stage C: Radiographic progression-free survival (rPFS）
The time from randomization or treatment initiation to the first documented radiographic disease progression or death from any cause, whichever occurs first. Tumor assessments are based on RECIST v1.1 and/or PCWG3.
Click on the lead sponsor to view all of their trials.
