A Clinical Study of QLC5508 and/or QLH12016 in Combinatio... | NCT07198633

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
QLC5508+NHA	Experimental	Drug: QLC5508 Drug: abiraterone acetate Drug: enzalutamide
QLC5508+QLH12016	Experimental	Drug: QLC5508 Drug: QLH12016
QLC5508+QLH12016+NHA	Experimental	Drug: QLC5508 Drug: abiraterone acetate Drug: enzalutamide Drug: QLH12016
QLH12016+NHA	Experimental	Drug: QLC5508 Drug: abiraterone acetate Drug: enzalutamide

Interventions

Name	Type	Description	Arm Group Labels	Other Names
QLC5508	Drug	B7H3 ADC; QLC5508 will be administered by injection at the dose and dosing frequency specified in the protocol.	QLC5508+NHA QLC5508+QLH12016

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	At the end of Day 28 after the first dose
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.	At the end of Day 28 after the first dose
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.	Through phase Ib completion, an average of 1 year.
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	Through phase Ib completion, an average of 1 year.
PSA50 response（Phase II）	Proportion of subjects with ≥ 50% PSA decrease	From Screening to confirmed progressive disease (approximately 1 year)
Objective response rate (ORR) (phase II)	Best response until progression, as defined by RECIST 1.1 and PCGW3.	From Screening to confirmed progressive disease (approximately 1 year)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
Histologically or cytologically confirmed adenocarcinoma of the prostate.
Radiologically confirmed metastatic prostate cancer.
For subjects with mCRPC, serum testosterone must be at castrate levels, and they must have demonstrated either PSA progression or radiographic progression.
Must have undergone surgical castration or be willing to receive medical castration.
For Phase Ib, subjects must have experienced failure, intolerance, or refusal of standard therapy.
Adequate function of major organs as defined by the protocol.
Agreement to use effective contraception during the study (except for subjects who have undergone bilateral orchiectomy).
Sufficient blood samples must be provided during the screening period for genetic mutation testing.

Exclusion Criteria:

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.
Presence of factors that may affect drug administration, intake, or absorption.
History of epilepsy, or a condition that could provoke seizures within 12 months prior to the first administration of the investigational medicinal product.
Known history of substance abuse, alcoholism, or drug addiction; or prior history of significant neurological or psychiatric disorders, including dementia or hepatic encephalopathy.
Presence of severe cardiovascular or cerebrovascular disease.
Active, uncontrolled infection.
Clinically uncontrolled third-space fluid accumulation prior to the first administration of the investigational medicinal product.
History of other malignancies within 5 years prior to the first administration of the investigational medicinal product.
Presence of moderate to severe pulmonary disease that significantly impairs lung function.
For subjects receiving QLC5508, history of non-infectious interstitial lung disease (ILD) or pneumonitis.

ID	Term
D000069501	Abiraterone Acetate
C540278	enzalutamide