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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 204
- 主要终点
- Stage I: the incidence of TEAE of HP568
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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-
- •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).
研究组 & 干预措施
HP568
In the I/II stage: HP568 administered QD or BID for 28 day cycles.
干预措施: HP568 (Drug)
HP568 and palbociclib
In the III stage: Daily oral dosages of HP568 for 28 days in combination with palbociclib for 21 days.
干预措施: HP568 in combination with palbociclib (Drug)
结局指标
主要结局
Stage I: the incidence of TEAE of HP568
时间窗: From the first administration dose to 30 calendar days after the last administration dose
the percentage of patients with treatment-emergent Adverse events(TEAE), TEAE will be evaluated using CTCAE 5.0 standards.
Stage I: Incidence of dose limiting toxicity DLT, maximum tolerated dose MTD (if possible).
时间窗: 28 days
First cycle dose-limiting toxicities and determination of a maximum tolerated dose (MTD) if applicable among the doses evaluated
Stage III: Evaluate safety during the dose escalation phase of combination therapy
时间窗: From the first administration dose to 30 calendar days after the last administration dose
Adverse events will be evaluated using the CTCAE5.0 standard, and safety features will be based on the assessment of adverse events, including TEAE, laboratory indicators (blood routine, blood biochemistry, coagulation routine, blood lipids, urine routine), vital sign measurements (blood pressure, pulse, respiratory rate, and body temperature), physical examination, and 12 lead electrocardiogram.
Stage III: Evaluate tolerance during the dose escalation phase of combination therapy
时间窗: 28 days
First cycle dose-limiting toxicities and determination of a maximum tolerated dose (MTD) if applicable among the doses evaluated
Stage III: Evaluate the 24 week clinical benefit rate (CBR) during the dose escalation phase of combination therapy
时间窗: Until all patients have completed 24 weeks administration
According to RECIST 1.1 criteria, the proportion of subjects who achieve confirmed CR (complete response) and/or confirmed PR (partial response) within 24 weeks plus at least 24 weeks of SD (stable disease).
Stage II: 24 week clinical benefit rate (CBR)
时间窗: Until all patients have completed 24 weeks administration
According to RECIST 1.1 criteria, the proportion of subjects who achieve confirmed CR (complete response) and/or confirmed PR (partial response) within 24 weeks plus at least 24 weeks of SD (stable disease).
次要结局
- Stage I-III: Objective response rate (ORR)(Until all patients have completed study（approximately 2 years）)
- Stage I/III: 24 week clinical benefit rate (CBR)(Until all patients have completed 24 weeks administration)
- Stage I-III: Disease Control Rate (DCR)(Until all patients have completed study（approximately 2 years）)
- Stage I-III: Progression free survival (PFS)(Until all patients have completed study（approximately 2 years）)
- Stage I-III: Duration of response(DOR)(Until all patients have completed study（approximately 2 years）)
- Stage I-III: Time to Response (TTR)(Until all patients have completed study（approximately 2 years）)
- Stage I-II：Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)(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)(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).(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)(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)(on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days))
- Stage III: Assessment of pharmacokinetic parameter maximum concentration (Cmax)(on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days))
- Stage III: Assessment of pharmacokinetic parameter minimum concentration (Cmin)(on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days))
- Stage III: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)(on the Day 1 and Day 21 of cycle 1 (each cycle is 28 days))