A Phase I/II Trial to Evaluate Oral HP568 Tablets in Patients with ER+/HER2 Advanced Breast Cancer

Официальное название

A Multicenter, Open, Dose Escalation/dose Escalation, and Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral HP568 Tablets Alone and in Combination with Palbociclib in Patients with ER+/HER2 Advanced Breast Cancer

Обзор

This is a Phase 1/2 dose escalation and cohort expansion study and will assess the safety, tolerability and preliminary efficacy of HP568 alone and in combination with palbociclib in patients with ER+/HER2- locally advanced or metastatic breast cancer.

Вмешательства

• Препарат HP568
  In the I/II stage: HP568 administered QD or BID for 28 day cycles.
• Препарат HP568 in combination with palbociclib
  In the III stage: Daily oral dosages of HP568 for 28 days in combination with palbociclib for 21 days.

Первичные конечные точки

• Stage I: the incidence of TEAE of HP568 [Срок оценки: From the first administration dose to 30 calendar days after the last administration dose]
• Stage I: Incidence of dose limiting toxicity DLT, maximum tolerated dose MTD (if possible). [Срок оценки: 28 days]
• Stage III: Evaluate safety during the dose escalation phase of combination therapy [Срок оценки: From the first administration dose to 30 calendar days after the last administration dose]
• Stage III: Evaluate tolerance during the dose escalation phase of combination therapy [Срок оценки: 28 days]
• Stage III: Evaluate the 24 week clinical benefit rate (CBR) during the dose escalation phase of combination therapy [Срок оценки: Until all patients have completed 24 weeks administration]
• Stage II: 24 week clinical benefit rate (CBR) [Срок оценки: Until all patients have completed 24 weeks administration]

Вторичные конечные точки (12)

• Stage I-III: Objective response rate (ORR) [Срок оценки: Until all patients have completed study（approximately 2 years）]
• Stage I/III: 24 week clinical benefit rate (CBR) [Срок оценки: Until all patients have completed 24 weeks administration]
• Stage I-III: Disease Control Rate (DCR) [Срок оценки: Until all patients have completed study（approximately 2 years）]
• Stage I-III: Progression free survival (PFS) [Срок оценки: Until all patients have completed study（approximately 2 years）]
• Stage I-III: Duration of response(DOR) [Срок оценки: Until all patients have completed study（approximately 2 years）]
• Stage I-III: Time to Response (TTR) [Срок оценки: Until all patients have completed study（approximately 2 years）]
• Stage I-II：Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC) [Срок оценки: on the first day of cycle 1 and cycle 2（each cycle is 28 days）]
• Stage I-II：Assessment of pharmacokinetic parameter maximum concentration (Cmax) [Срок оценки: on the first day of cycle 1 and cycle 2（each cycle is 28 days）]
• Stage I-II: Assessment of pharmacokinetic parameter minimum concentration (Cmin). [Срок оценки: on the first day of cycle 1 and cycle 2 (each cycle is 28 days)]
• Stage I-II：Assessment of pharmacokinetic parameter time to maximum concentration (Tmax) [Срок оценки: on the first day of cycle 1 and cycle 2 (each cycle is 28 days)]
• Stage III：Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC) [Срок оценки: on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days)]
• Stage III: Assessment of pharmacokinetic parameter maximum concentration (Cmax) [Срок оценки: on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days)]

Критерии участия

Критерии включения

• Women aged 18-75 years old (inclusive of both ends) at the time of signing the informed consent form.
• Patients with locally advanced inoperable or recurrent or metastatic breast cancer ER+/HER2- advanced breast cancer is confirmed by histopathology have confirmed that the primary and/or metastatic lesion.
• Previously received at least 1-line endocrine therapy (endocrine therapy duration ≥ 6 months) and ≤ 2-line chemotherapy (≤ 2-line chemotherapy limited to dose escalation stage) for the recurrence or metastasis stage of the disease. The third stage : Inclusion of patients who have not received prior treatment but are suitable for CDK4/6i therapy.
• Disease progression confirmed by imaging occurs during or after the last systemic anti-tumor treatment before the first medication.

Критерии исключения

• Known or suspected allergy to any ingredient of HP568 formulation, and allergy to any ingredient of palbociclib (only applicable to stage III).
• Within 42 days prior to the first administration, Fluvistran was used; Other endocrine therapies such as tamoxifen, toremifene, letrozole, anastrozole, and exemestane were used within 14 days prior to the first administration.
• Previously received other ER-ROTAC drugs such as ARV-471.
• Within 6 weeks before the first administration of HP568 in this study, nitrosoureas or mitomycin were used; Received any anti-tumor treatment, including immunotherapy, chemotherapy, radiotherapy, or targeted therapy, within 28 days prior to the first administration (or of the drug's 5 half lives,take the shorter one).

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06757335 · HP568-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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