Ph 1/1b/2 Multicenter, Open-Label, FIH Dose Esc & Dose Exp Study to Assess Safety and Tolerability of Orally Administered PMD-026 as a Single Agent and in Combination in Patients With Metastatic or Locally Advanced (Inoperable) RSK2+ Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 61
- 试验地点
- 21
- 主要终点
- Safety and tolerability of PMD-026 in combination with fulvestrant in patients with HR+/HER2- previously treated breast cancer
研究概览
简要总结
The purpose of this study is to test the safety and tolerability of PMD-026 in patients with metastatic breast cancer. PMD-026 is a targeted oral agent designed to kill tumor cells in metastatic breast cancer.
详细描述
Combination with fulvestrant (Part 3):
This study will enroll RSK2+, HR+, and human epidermal growth factor receptor 2 negative (HER2-) patients to evaluate PMD-026 in combination with a standard dose and schedule of fulvestrant. Fulvestrant will be dosed per the package insert in combination with PMD-026 at the RP2D determined in the monotherapy phase of the study. Up to 20 patients will be enrolled with locally advanced or metastatic HR+/HER2- breast cancer previously treated with a CDK4/6 inhibitor in combination with endocrine therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •, Combination with fulvestrant (Part 3):
- •RSK2 positive from available archival or fresh tumor tissue (FFPE).
- •Histologically or cytologically diagnosed HR+, HER2-
- •ESR1 wild type
- •Diagnosis of adenocarcinoma of the breast with evidence of either locally advanced disease not amendable to resection or radiation with curative intent or metastatic disease not amendable to curative therapy
- •Must be appropriate candidates for endocrine therapy
- •Previously received at least 1 line of endocrine therapy for MBC or had recurrence while on adjuvant endocrine therapy for locally advanced breast cancer
- •Discontinued endocrine therapy at least 15 days prior to first dose of PMD-026
- •At least 1 measurable target lesion as defined by RECIST v1.1
- •Progression on or after treatment with a CDK4/6 inhibitor in combination with endocrine therapy inhibitor in the locally advanced or metastatic setting
- •Adequate hematologic, hepatic, and renal function as assessed by laboratory parameters
- •Toxicity related to prior therapy resolved to at least Grade 1 (alopecia excepted) or to at least Grade 2 with prior approval of the Medical Monitor
排除标准
- •, Combination with fulvestrant (Part 3):
- •Prior chemotherapy
- •ESR1 mutations
- •≤14 days from biological or investigational therapy
- •Presence of visceral crisis or uncontrolled visceral disease for which chemotherapy would be indicated
- •Central nervous system metastases, unless appropriately treated and neurologically stable
- •History of leptomeningeal metastases
- •Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- •Known hepatitis B or hepatitis C infection
- •Known HIV-positive with CD4+ cell counts <350 cells/μL
- •Known HIV-positive with a history of an AIDS-defining opportunistic infection
- •History of clinically significant cardiovascular abnormalities, including QTcF interval >460 msec (using Fridericia's formula)
研究组 & 干预措施
Oral PMD-026 in combination with fulvestrant
Daily dosing of PMD-026 with fulvestrant dosing according to package insert
干预措施: PMD-026 (Drug)
Oral PMD-026 in combination with fulvestrant
Daily dosing of PMD-026 with fulvestrant dosing according to package insert
干预措施: fulvestrant (Drug)
结局指标
主要结局
Safety and tolerability of PMD-026 in combination with fulvestrant in patients with HR+/HER2- previously treated breast cancer
时间窗: 6 weeks
Incidence of AEs, DLTs, SAEs. Changes in laboratory, vital signs, and ECG values.
次要结局
- Plasma concentration of PMD-026 when administered in combination with fulvestrant(As determined by PK data)
- Preliminary anti-tumor activity of PMD-026 when dosed in combination with fulvestrant(Until PD or death, up to 2 years)