A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients

Официальное название

A Phase I/II Open-Label Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer in China

Обзор

The overall objective of this Phase 1 study is to evaluate the safety, PK,and anti-tumor activity of daily oral dosing with HP518,selecting the RP2D of HP518 based on assessments of patients with progressive mCRPC in dose-escalation phase

Подробное описание

This First in Human dose escalation and expansion study of HP518 in patients with progressive mCRPC after NHA and chemotherapy is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide preliminary efficacy for the reference of future studies.

Вмешательства

• Препарат HP518 - Dose Escalation
  Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort
• Препарат HP518 - Dose Escalation
  Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort
• Препарат HP518 -Dose Expansion
  Part 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.

Первичные конечные точки

• Incidences of Protocol-defined DLT during the DLT assessment period , characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drugorally administered HP518 (Part 1) [Срок оценки: 28 DAYS]
• Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness [Срок оценки: Through study completion, an average of 1 year]
• Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing [Срок оценки: Through study completion, an average of 1 year]
• Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing [Срок оценки: Through study completion, an average of 1 year]
• Incidence of ECG (PR, QRS, QT, and QTcF intervals) abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing [Срок оценки: Through study completion, an average of 1 year]
• PSA50 response rate [Срок оценки: 12 weeks]

Вторичные конечные точки (11)

• area under the concentration-time curve (AUC) [Срок оценки: 12 weeks]
• Maximum concentration (Cmax) [Срок оценки: 12 weeks]
• Time to maximum concentration (Tmax) [Срок оценки: 12 weeks]
• Apparent terminal elimination half-life (T1/2) [Срок оценки: 12 weeks]
• apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) [Срок оценки: 12 weeks]
• oral clearance (CL/F) [Срок оценки: 12 weeks]
• According to PCWG3 [Срок оценки: 8 weeks]
• According to PCWG3, evaluate time to PSA progression [Срок оценки: Through study completion, an average of 1 year]
• Time to radiographic progression by investigator PCWG3 definition [Срок оценки: Through study completion, an average of 1 year]
• Evaluate the modified best overall response mBOR by investigator [Срок оценки: Through study completion, an average of 1 year]
• analyze the efficacy of patients with different AR phenotypes(Part 2) [Срок оценки: Through study completion, an average of 1 year]

Критерии участия

Критерии включения

• Male, age ≥18
• Patients with androgen receptor (AR) ligand binding domain (LBD) activation mutations (the dose expansion part of stage II)
• Has histologically confirmed adenocarcinoma of the prostate, but there are no known significant neuroendocrine differentiation or small cell characteristics.
• Has metastatic disease documented by 2 or more bone lesions by bone scan or soft tissue disease progression observed by CT/MRI at the beginning of study.
• the progression of the disease after receiving at least one new endocrine therapy and progressing with at least first-line chemotherapy.
• Must have recovered from toxicities related to any prior treatments
• Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy.
• ECOG performance status score of 0 to 1.

Критерии исключения

• Combination of research or commercially available drugs targeting AR
• Has had any other anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177LuPSMA-617, radium 223, PARP inhibitor) within 4 weeks prior to the first dose of HP518.
• Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).
• Has significant cardiovascular disease.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 27 центров

• The Second Hospital Of Anhui Medical University — Хэфэй
• Beijing Cancer Hospital — Пекин
• Beijing Friendship Hospital, Capital Medical University — Пекин
• Chongqing University Cancer Hospital — Чунцин
• The Second Affiliated Hospital Of Chongqing Medical University — Чунцин
• The First Affiliated Hospital Of Xiamen Univeristy — Xiamen
• Lanzhou University Second Hospital — Lanzhou
• The Third Affiliated Hospital of Southern Medical University — Гуанчжоу
• … и ещё 19 центров

Идентификаторы

NCT: NCT06155084 · HP518-01-01-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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