A Multicenter, Open-label, Dose Escalation, Phase I Study of LJM716 Administered Intravenously in Combination With Trastuzumab in Patients With HER2 Overexpressing Metastatic Breast Cancer or Gastric Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Incidence rate of Dose Limiting Toxicities
研究概览
简要总结
This is a multicenter, open-label, dose escalation, phase I study to estimate the Maximum Tolerated Dose (MTD) or a lower Recommended Dose for Expansion (RDE) of LJM716 in combination with trastuzumab in patients with Human Epidermal growth factor Receptor 2 (HER2) overexpressing Metastatic Breast Cancer (MBC) or gastric cancer (MGC). The study consists of a dose escalation part and a dose expansion part. LJM716 will be administered intravenously once weekly unless a less frequent dosing regimen such as every 2 weeks or once every 4 weeks is introduced. Patients will continue on their trastuzumab dosing, administered intravenously once weekly at 2mg/kg. During dose escalation, a minimum of 15 patients are anticipated to be treated in successive cohorts. The dose escalation will continue until the MTD/RDE is declared. The RDE dose selected will either be the MTD or a dose below the MTD based on safety and Pharmacokinetic/Pharmacodynamic (PK/PD) considerations. Following the MTD/RDE declaration, approximately 20 MBC and 20 MGC patients will be enrolled in separate arms in the dose expansion part and treated at the MTD/RDE to further assess the safety, tolerability, and anti-tumor activity of the combination.
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
- •Patients with confirmed HER-2 positive, metastatic or non-operable locally advanced breast or gastric cancer
- •Metastatic breast cancer patients must have received a minimum of 1 and a maximum of 3 prior anti HER2 based regimens with documented progression on the most recent regimen which must contain trastuzumab, ado-trastuzumab emtansine or lapatinib
- •Metastatic gastric cancer patients must have received a minimum of 1 and a maximum of 2 prior anti HER2 based regimens with documented progression on the most recent regimen which must contain trastuzumab or ado-trastuzumab emtansine
- •During the dose expansion part of study, all patients must have at least one measurable lesion as defined by RECIST criteria.
- •Patients must have at least one prior trastuzumab-containing regimen
- •Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2
排除标准
- •Patients with Central Nervous System (CNS) metastasis which are: symptomatic or require treatment for symptom control and/or growing
- •Prior treatment with any anti-HER3 (Human Epidermal growth factor Receptor 3) treatment
- •Impaired cardiac function
- •Prior to the first dose of study treatment, patients who have received systemic antineoplastic therapy or any investigational therapy within 4 weeks or within 5 half- lives of the therapy prior to starting study treatment, whichever is shorter, or for cyclical therapy, within one cycle length (e.g. 6 weeks for nitrosourea, mitomycin-C).
- •Patients who have a history of primary malignancy other than that being treated in this study, and currently requires active clinical intervention.
- •Patients who do not have an archival tumor sample (or sections of it) available or readily obtainable.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
LJM716 in combination with trastuzumab
干预措施: LJM716 (Drug)
LJM716 in combination with trastuzumab
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Incidence rate of Dose Limiting Toxicities
时间窗: 4 weeks
Incidence of dose-limiting toxicities (DLTs)
次要结局
- Number of adverse events(4 months)
- Number of serious adverse events(4 months)
- Pharmacodynamic response to LJM716 in tumor tissue(3 months)
- Progression-free survival(18 months)
- Serum concentration of anti-LJM716 antibodies(4 months)
- Serum concentration of LJM716 when administered in combination with trastuzumab(4 months)
- Duration of response(18 months)
- Frequency of partial responses according to Response Evaluation Criteria In Solid Tumors (RECIST)(every 2 months up to 18 months)
- Frequency of complete responses according to RECIST(every 2 months up to 18 months)
- Frequency of stable disease according to RECIST(every 2 months up to 18 months)