Phase Ib Study of HS-20093+HRS-5041 in Patients With Advanced Prostate Cancer

Официальное название

A Phase Ib Study to Explore the Safety, Tolerability, and Pharmacokinetics of HS-20093 Combination With HRS-5041 in Patients With Advanced Prostate Cancer

Обзор

HS-20093 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. HRS-5041 is a Proteolysis Targeting Chimeras (PROTAC) targeting androgen receptors. This is a phase Ib, open-label, multi-center study to evaluate the safety, tolerability, and pharmacokinetics (PK) of HS-20093 combination with HRS-5041 in patients with advanced prostate cancer.

Вмешательства

• Препарат HS-20093
  Intravenous (IV) administration of HS-20093 Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.
• Препарат HRS-5041
  HRS-5041 was given oral administration, QD, at a 21-day cycle.

Первичные конечные точки

• To determine the maximum tolerated dose (MTD) or Maximum Administrated dose (MAD) [Срок оценки: 21 days from administration of the first dose (C1D1) in the dose escalation phase， assessed up to 24 months]

Вторичные конечные точки (10)

• To evaluate the incidence and severity of adverse events (AEs) [Срок оценки: From the first dose(C1D1) up to 30 days after the last dose of HRS-5041 or 90 days after the last dose of HS-20093 (whichever is later)]
• To evaluate the maximum plasma concentration (Cmax) [Срок оценки: up to approximately 24 months]
• To evaluate the Time to reach maximum plasma concentration (Tmax) [Срок оценки: up to approximately 24 months]
• To evaluate the Area under plasma concentration versus time curve from zero to last sampling time (AUC) [Срок оценки: up to approximately 24 months]
• To evaluate the immunogenicity of HS-20093 [Срок оценки: up to approximately 24 months]
• To evaluate the ORR determined by investigators [Срок оценки: up to approximately 24 months]
• To evaluate the Disease control rate (DCR) determined by investigators according to RECIST 1.1 and PCWG3 [Срок оценки: up to approximately 24 months]
• To evaluate the Duration of response (DoR) determined by investigators according to RECIST 1.1 and PCWG3 [Срок оценки: up to approximately 24 months]
• To evaluate the Prostate-specific Cancer Antigen (PSA) response rate（PSA30,PSA50,PSA90） [Срок оценки: up to approximately 24 months]
• To evaluate the Time to PSA progression [Срок оценки: up to approximately 24 months]

Критерии участия

Критерии включения

• Men greater than or equal to 18 years.
• Voluntarily to participate, Signed and dated Informed Consent Form.
• Patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after at least one type of novel hormonal therapy (standard treatment).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1.
• Estimated life expectancy ≥ 12 weeks.
• Men should use adequate contraceptive measures throughout the study, up to 3 months after the last dose of HRS-5041 or 4.5 months after the last dose of HS-20093 (whichever is later).

Критерии исключения

• Treatment with any of the following:

a. Previous or current treatment with B7-H3 targeted therapy. b. Previous treatment with AR PROTAC. c. Any cytotoxic chemotherapy, investigational agents and anticancer drugs within 21 days prior to the first scheduled dose of HS-20093+HRS-5041. d. brain metastases.

• Any unresolved toxicities from prior therapy greater than Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
• History of other primary malignancies.
• Inadequate bone marrow reserve or organ dysfunction.
• Severe, uncontrolled or active cardiovascular diseases.
• Severe or uncontrolled diabetes.
• The presence of active infectious diseases.
• Any known or suspected interstitial lung disease.
• History of serious neuropathy or mental disorders.
• History of severe hypersensitivity reaction, severe infusion reaction.
• Hypersensitivity to any ingredient of HS-20093.
• Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator.
• Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07115446 · HS-20093-107

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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