A Phase 1B Dose Escalation Trial of Human Anti 4 1BB Agonistic Antibody Utomilumab (PF 05082566) in Combination With Ado Trastuzumab Emtansine or Trastuzumab in Patients With HER2 Postive Advanced Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This trial studies the best dose and side effects of utomilumab (4-1BB agonist monoclonal antibody PF-05082566) with trastuzumab emtansine or trastuzumab in treating patients with HER2-positive breast cancer that has spread to other places in the body. Monoclonal antibodies, such as utomilumab, trastuzumab emtansine, and trastuzumab may interfere with the ability of tumor cells to grow and spread.
详细描述
PRIMARY OBJECTIVE:
Estimate the maximum tolerated dose (MTD) and determine the recommended dose (RP2D) of utomilumab in combination with ado-rastuzumab emtansine (T-DM1) or trastuzumab in subjects with HER2-positive advanced breast cancer.
SECONDARY OBJECTIVES:
- Determine the objective tumor response (ORR)
- Determine the time to tumor response (TTR)
- Determine the duration of response (DR)
- Determine progression free survival (PFS)
- Assess the safety and tolerability of utomilumab in combination with ado-trastuzumab emtansine or trastuzumab
OUTLINE: Patients are randomized to 1 of 2 cohorts.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1A (trastuzumab + utomilumab)
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
干预措施: Utomilumab (Drug)
Cohort 1A (trastuzumab + utomilumab)
Utomilumab 20 mg IV + trastuzumab 6 mg/kg IV every 3 weeks. 3 subjects will be treated at this dose level. If no DLT events are recorded, then utomilumab dose will be increased to 100 mg (Dose Level 1B).
干预措施: Trastuzumab (Drug)
Cohort 1B (trastuzumab + utomilumab)
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
干预措施: Utomilumab (Drug)
Cohort 1B (trastuzumab + utomilumab)
Utomilumab 100 mg IV + trastuzumab 6 mg/kg IV every 3 weeks.
干预措施: Trastuzumab (Drug)
Cohort 2A (ado-trastuzumab emtansine + utomilumab)
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
干预措施: Utomilumab (Drug)
Cohort 2A (ado-trastuzumab emtansine + utomilumab)
Utomilumab 20 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
干预措施: Ado-Trastuzumab Emtansine (Drug)
Cohort 2B (ado-trastuzumab emtansine + utomilumab)
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
干预措施: Utomilumab (Drug)
Cohort 2B (ado-trastuzumab emtansine + utomilumab)
Utomilumab 100 mg IV + ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks.
干预措施: Ado-Trastuzumab Emtansine (Drug)
结局指标
主要结局
Dose-limiting Toxicities (DLTs)
时间窗: 6 weeks
Dose-limiting toxicities (DLTs) within the first 2 cycles (6 weeks) of treatment were assessed. DLTs are treatment-related adverse events defined as: * Neutropenia Grade (Gr) 4 \>7 days * Febrile neutropenia, defined as absolute neutrophil count \<1000/mm3 with a single temperature of \>38.3 degrees C (101 degrees F) or a sustained temperature of ≥38 degrees C (100.4 degrees F) for \>1 hour * Neutropenic infection ≥Gr 3 * Thrombocytopenia ≥Gr 4, or with bleeding Gr 3 * Non-laboratory toxicities ≥Gr 3, except nausea, vomiting, or diarrhea recovering to \<Gr 2 within 48 hours. * Laboratory abnormalities \[other than aspartate aminotransferase / alanine aminotransferase (AST/ALT)\] ≥Gr 3, if: * Medical intervention required * Hospitalization required, or * \>24 hours * AST \& ALT Gr 4, or \>3×ULN * Total bilirubin \>2×ULN, with no elevation of alkaline phosphatase The outcome is reported as the number of DLTs observed per group, a number with dispersion.
次要结局
- Progression-free Survival (PFS)(128 weeks)
- Duration of Response (DoR)(up to 260 weeks)
- Objective Tumor Response (ORR)(3 months)
- Adverse Event Relationship to Study Drugs(Up to 128 weeks)
- Time-to-tumor Response (TTR)(3 months)
- Adverse Events by Severity Grade 1 to 5(Up to 128 weeks)
研究者
George W. Sledge Jr.
Principal Investigator
Stanford University