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

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tianjin Medical University Cancer Institute & Hospital — Tianjin

Identifiers

NCT: NCT07198633 · QLC5508-202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗