This study is an open-label, multicenter Phase Ib/II clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of QLC5508 in combination with NHA (abiraterone or enzalutamide), QLC5508 in combination with QLH12016, QLC5508 in combination with QLH12016 and NHA (abiraterone or enzalutamide), and QLH12016 in combination with NHA (abiraterone or enzalutamide) in subjects with advanced prostate cancer.
The study consists of two stages:
Phase Ib: is the combination dose-escalation stage, during which the recommended Phase II dose (RP2D) will be determined.
Phase II is the efficacy exploration stage, in which, based on the RP2D established in Phase Ib, the therapeutic efficacy will be further evaluated in the target indication.
The subject voluntarily agrees to participate and has signed the informed consent form.
Male, aged ≥18 years.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
Life expectancy of at least 3 months.
Prior treatment with the following agents: AR PROTAC, abiraterone, enzalutamide, or B7H3-targeted therapies.
Presence of central nervous system (CNS) metastases, leptomeningeal metastases, or spinal cord compression requiring hormonal therapy.
Receipt of extensive radiotherapy within 4 weeks prior to the first administration of the investigational medicinal product.
Treatment with other investigational drugs or major surgery within 4 weeks prior to the first administration of the investigational medicinal product.
Single group
QLC5508
DrugB7H3 ADC; QLC5508 will be administered by injection at the dose and dosing frequency specified in the protocol.
abiraterone acetate
DrugAn oral CYP17 inhibitor; abiraterone acetate will be administered orally at the dose and dosing frequency specified in the protocol
enzalutamide
DrugAn oral androgen receptor inhibitor; enzalutamide will be administered orally at the dose and dosing frequency specified in the protocol.
QLH12016
DrugAn oral androgen receptor PROTAC; QLH12016 will be administered orally at the dose and dosing frequency specified in the protocol
Maximum tolerated dose (MTD) (Phase Ib)
MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a DLT
Maximum administered dose (MAD)(Phase Ib)
MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the PK-PD model, it suggested that the optimal target concentration of safety and efficacy has been explored.
recommended phase II dose (RP2D) (Phase Ib)
The RP2D will be comprehensively evaluated based on the safety, PK characteristics, and efficacy data from the Phase Ib study.
The incidence and severity of adverse events (AE) (Phase Ib)
Incidence and severity of adverse events (AEs) evaluated according to the NCI-CTCAE v5.0
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