A Phase 3, Randomized Study of Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of Patients With HER2+ Metastatic Breast Cancer Who Have Received Prior Anti-HER2 Therapies and Require Systemic Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 624
- 试验地点
- 165
- 主要终点
- Progression-free Survival (PFS) as Determined by Independent Radiological Review.
研究概览
简要总结
The purpose of this study is to determine whether patients with metastatic breast cancer treated with margetuximab plus chemotherapy have longer progression free survival (PFS) and overall survival (OS) than patients treated with trastuzumab plus chemotherapy.
A non-randomized sub-study cohort of approximately 88 patients will be enrolled to evaluate the safety of a reduced margetuximab infusion rate in patients receiving margetuximab either as monotherapy or in combination with chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically-proven metastatic or locally-advanced relapsed/refractory HER2+ breast cancer based on the most recently available tumor biopsy collected from the patient. Tumors may be estrogen receptor (ER)/progesterone receptor (PgR) positive or negative.
- •Have received at least 2 prior lines of anti-HER2 directed therapy in the metastatic setting, or in case of having received (neo)adjuvant pertuzumab, at least 1 prior line of anti-HER2 directed therapy in the metastatic setting. In either case, patients must have received prior treatment with pertuzumab, in the (neo)adjuvant or metastatic setting. Prior radiotherapy, hormonal therapies, and other anti-HER2 therapies are allowed.
- •Prior treatment with at least one, and no more than three, lines of therapy overall in the metastatic setting. Patients must have progressed on or following, the most recent line of therapy.
- •Resolution of all chemotherapy or radiation-related toxicities to ≤ Grade 1
- •Life expectancy ≥ 12 weeks
- •Acceptable laboratory parameters
- •Women of childbearing potential must have negative pregnancy test performed within 14 days of randomization and on the first day of treatment. All subjects must agree to use an effective form of contraception for the duration of study treatment and for 7 months after the last dose of study drug.
- •Infusion sub-study prior therapy requirements: Same as above, except:
- •Must have received 4 or more prior lines or therapy in the metastatic setting
- •Must have received prior trastuzumab, pertuzumab, and T-DM1
排除标准
- •Known, untreated brain metastasis. Patients with signs or symptoms of brain metastasis must have a CT or MRI performed within 4 weeks prior to randomization to specifically exclude the presence of radiographically-detected brain metastases
- •History of uncontrolled seizures within 6 months of randomization
- •History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation
- •History of clinically significant cardiovascular disease
- •Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation
- •Any condition that would be a contraindication to receiving trastuzumab as described in the approved local label or a condition that would prevent treatment with the physician's choice of chemotherapy
研究组 & 干预措施
Margetuximab plus chemotherapy
Margetuximab 15 mg/kg every 21 days
干预措施: Margetuximab (Biological)
Margetuximab plus chemotherapy
Margetuximab 15 mg/kg every 21 days
干预措施: Physician's choice of chemotherapy. (Drug)
Trastuzumab plus chemotherapy
Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days
干预措施: Trastuzumab (Biological)
Trastuzumab plus chemotherapy
Trastuzumab 8 mg/kg loading dose, then 6 mg/kg every 21 days
干预措施: Physician's choice of chemotherapy. (Drug)
Margetuximab Infusion Sub-study
Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2.
干预措施: Margetuximab (Biological)
Margetuximab Infusion Sub-study
Margetuximab 15 mg/kg every 21 days (with or without chemotherapy), studying a shorter duration of infusion beginning in Cycle 2.
干预措施: Physician's choice of chemotherapy. (Drug)
结局指标
主要结局
Progression-free Survival (PFS) as Determined by Independent Radiological Review.
时间窗: Tumor assessments are conducted every 6 weeks for the first 24 weeks and then every 24 weeks until progression of cancer, average 5 months.
PFS is measured from the time of randomization until first documented disease progression or death from any cause, whichever is first.
Overall Survival (OS) Defined as the Number of Days From Randomization to the Date of Death (From Any Cause).
时间窗: Throughout the study, average 21 months
Overall survival is the time from randomization until death from any cause
Number of Patients With Grade 3 or Higher Infusion Related Reactions
时间窗: 22 days
Incidence of Grade 3 or higher infusion-related reactions for patients receiving 60-minute or 30-minute infusions of margetuximab in Cycle 2 of treatment
次要结局
- To Evaluate Progression-free Survival (PFS), as Assessed by Study Investigators.(Tumor assessments are conducted every 6 weeks for the first 24 weeks and then every 24 weeks until progression of cancer, up to 6.5 years.)
- To Evaluate the Objective Response Rate (ORR) as Determined by Independent Radiological Review.(Tumor assessments are conducted every 6 weeks for the first 24 weeks and then every 24 weeks until progression of cancer, up to 6.5 years.)
- Infusion Rate Sub-study All Safety(Throughout the study, average duration 6 months)