A Clinical Study of QLC5508 and/or QLH12016 in Combination With Other Anti-tumor Therapies in Subjects With Advanced Prostate Cancer

Официальное название

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

Обзор

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.

Вмешательства

• Препарат QLC5508
  B7H3 ADC; QLC5508 will be administered by injection at the dose and dosing frequency specified in the protocol.
• Препарат abiraterone acetate
  An oral CYP17 inhibitor; abiraterone acetate will be administered orally at the dose and dosing frequency specified in the protocol
• Препарат enzalutamide
  An oral androgen receptor inhibitor; enzalutamide will be administered orally at the dose and dosing frequency specified in the protocol.
• Препарат QLH12016
  An oral androgen receptor PROTAC; QLH12016 will be administered orally at the dose and dosing frequency specified in the protocol

Первичные конечные точки

• Maximum tolerated dose (MTD) (Phase Ib) [Срок оценки: At the end of Day 28 after the first dose]
• Maximum administered dose (MAD)(Phase Ib) [Срок оценки: At the end of Day 28 after the first dose]
• recommended phase II dose (RP2D) (Phase Ib) [Срок оценки: Through phase Ib completion, an average of 1 year.]
• The incidence and severity of adverse events (AE) (Phase Ib) [Срок оценки: Through phase Ib completion, an average of 1 year.]
• PSA50 response（Phase II） [Срок оценки: From Screening to confirmed progressive disease (approximately 1 year)]
• Objective response rate (ORR) (phase II) [Срок оценки: From Screening to confirmed progressive disease (approximately 1 year)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tianjin Medical University Cancer Institute & Hospital — Тяньцзинь

Идентификаторы

NCT: NCT07198633 · QLC5508-202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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