A Prospective Phase Ib Study of Anlotinib With Trastuzumab Deruxtecan for HER2-Low Unresectable and/or Metastatic Breast Cancer (ALTER-BC-Ib-01)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
A Prospective Phase Ib Study of Anlotinib with Trastuzumab Deruxtecan for HER2-Low Unresectable and/or Metastatic Breast Cancer
详细描述
This study will evaluate the safety, tolerability and efficacy of anlotinib and trastuzumab deruxtecan in human epidermal growth factor receptor 2 (HER2)-low unresectable and/or metastatic breast cancer who had received ≤1 line of prior chemotherapy.
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
- •Age 18 - 75 years;
- •ECOG PS 0 or
- •. Pathologically documented breast cancer that:
- •(1) Is unresectable or metastatic. (2) Has a history of low HER2 expression (IHC 1+& IHC 2+/ISH- or 0<IHC<1+). (3) Is HR-positive or HR-negative. (4) Has progressed on, and would no longer benefit from, endocrine therapy. (5) Has been treated with ≤ 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting.
- •At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.
- •Has protocol-defined adequate bone marrow, renal, hepatic and blood clotting functions.
- •Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and after the last dose for at least 6 months.
排除标准
- •Has previously been treated with anti-angiogenic targeted small molecule therapy.
- •Prior treatment with antibody drug conjugate with a topoisomerase I inhibitor exatecan derivative.
- •Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Has unresolved toxicities from previous anticancer therapy.
- •Has uncontrolled or significant cardiovascular disease.
- •Has any bleeding event, unhealed wounds, ulcerative or fractures.
- •Has arterial or venous thromboembolic events occurred within 6 months.
- •Has spinal cord compression or clinically active central nervous system metastases.
- •Has any other condition that per protocol or in the opinion of the investigator is inappropriate for the study.
研究组 & 干预措施
Anlotinib dose escalation + trastuzumab deruxtecan
Various doses of anlotinib (8 mg QD, 10 mg QD, and 12 mg QD) administered during dose escalation to determine the recommended phase 2 Dose (RP2D) + trastuzumab deruxtecan 5.4 mg/kg.
Anlotinib at the RP2D + trastuzumab deruxtecan 5.4 mg/kg combination therapy
干预措施: Anlotinib (Drug)
Anlotinib dose escalation + trastuzumab deruxtecan
Various doses of anlotinib (8 mg QD, 10 mg QD, and 12 mg QD) administered during dose escalation to determine the recommended phase 2 Dose (RP2D) + trastuzumab deruxtecan 5.4 mg/kg.
Anlotinib at the RP2D + trastuzumab deruxtecan 5.4 mg/kg combination therapy
干预措施: Trastuzumab deruxtecan (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to approximately 3 years
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Determination of the RP2D of anlotinib in combination with trastuzumab deruxtecan
时间窗: up to 1 year
The RP2D is defined as the dose level for the dose expansion phase, based on safety, tolerability, efficacy collected during the dose escalation portion of the study.
次要结局
- Duration of Response (DCR)(Up to approximately 3 years)
- Duration of Response (DOR)(Up to approximately 3 years)
- Progression-free Survival (PFS)(Up to approximately 3 years)
- Overall Survival (OS)(Up to approximately 3 years)
- Number of Participants With Adverse Events (AEs)(Up to approximately 3 years)
研究者
Jian Zhang,MD
Director of Phase I Clinical Trial Department; Professor, Chief physician of oncology department
Fudan University