An Open-label, Multicenter Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of QLC5508 and/or QLH12016 in Combination With Other Anti-tumor Therapies in Subjects With Advanced Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 212
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) (Phase Ib)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
QLC5508+QLH12016+NHA
干预措施: QLC5508 (Drug)
QLC5508+QLH12016
干预措施: QLC5508 (Drug)
QLC5508+NHA
干预措施: QLC5508 (Drug)
QLH12016+NHA
干预措施: QLC5508 (Drug)
QLC5508+NHA
干预措施: abiraterone acetate (Drug)
QLC5508+NHA
干预措施: enzalutamide (Drug)
QLC5508+QLH12016
干预措施: QLH12016 (Drug)
QLC5508+QLH12016+NHA
干预措施: abiraterone acetate (Drug)
QLC5508+QLH12016+NHA
干预措施: enzalutamide (Drug)
QLC5508+QLH12016+NHA
干预措施: QLH12016 (Drug)
QLH12016+NHA
干预措施: abiraterone acetate (Drug)
QLH12016+NHA
干预措施: enzalutamide (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) (Phase Ib)
时间窗: At the end of Day 28 after the first dose
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)
时间窗: At the end of Day 28 after the first dose
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)
时间窗: Through phase Ib completion, an average of 1 year.
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)
时间窗: Through phase Ib completion, an average of 1 year.
Incidence and severity of adverse events (AEs) evaluated according to the NCI-CTCAE v5.0
PSA50 response（Phase II）
时间窗: From Screening to confirmed progressive disease (approximately 1 year)
Proportion of subjects with ≥ 50% PSA decrease
Objective response rate (ORR) (phase II)
时间窗: From Screening to confirmed progressive disease (approximately 1 year)
Best response until progression, as defined by RECIST 1.1 and PCGW3.
次要结局
未报告次要终点