A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) Administered Intravenously as a Single Agent to Patients With Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 661
- 试验地点
- 21
- 主要终点
- Maximum Tolerated Dose (MTD) of Atezolizumab
研究概览
简要总结
This Phase I, multicenter, first-in-human, open-label, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of atezolizumab (MPDL3280A) administered as single agent to participants with locally advanced or metastatic solid malignancies or hematologic malignancies. The study will be conducted in two cohorts: Dose-escalation cohort and Expansion cohort.
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
- •Participants who are 16 to 17 years old would be enrolled after consultation with the Medical Monitor
- •Histologically or cytologically documented, incurable or metastatic solid tumor or hematologic malignancy that is advanced (non-resectable) or recurrent and progressing since the last anti-tumor therapy and for which no recognized standard curative therapy exists
- •Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report
- •Adequate hematologic and end organ function
- •Measurable disease per RECIST v1.1 for participants with solid malignancies. Disease-specific criteria for participants with prostate cancer, glioblastoma multiforme (GBM), malignant lymphoma, or multiple myeloma
- •For women of childbearing potential: agreement to remain abstinent or use contraceptive methods
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •For participants who will undergo serial biopsy in dose-escalation cohort, baseline tumor tissue samples should be of core needle biopsies for deep tumor tissue or organs or excisional or punch biopsies for cutaneous or subcutaneous lesions (>/=5 millimeter [mm] in diameter amenable to serial biopsy)
排除标准
- •Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
- •Known hypersensitivity to pharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- •History or risk of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis)
- •History of human immunodeficiency virus (HIV) infection, active hepatitis B (chronic or acute), or hepatitis C infection
- •Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
- •Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1
- •Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation
研究组 & 干预措施
Dose Escalation Cohort: Atezolizumab 0.01 mg/kg
Participants will receive intravenous (IV) infusion of atezolizumab 0.01 milligrams per kilogram (mg/kg) every 3 weeks (q3w) until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
干预措施: Atezolizumab (Drug)
Dose Escalation Cohort: Atezolizumab 0.03 mg/kg
Participants will receive IV infusion of atezolizumab 0.03 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
干预措施: Atezolizumab (Drug)
Dose Escalation Cohort: Atezolizumab 0.1 mg/kg
Participants will receive IV infusion of atezolizumab 0.1 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
干预措施: Atezolizumab (Drug)
Dose Escalation Cohort: Atezolizumab 0.3 mg/kg
Participants will receive IV infusion of atezolizumab 0.3 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
干预措施: Atezolizumab (Drug)
Dose Escalation Cohort: Atezolizumab 1 mg/kg
Participants will receive IV infusion of atezolizumab 1 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
干预措施: Atezolizumab (Drug)
Dose Escalation Cohort: Atezolizumab 3 mg/kg
Participants will receive IV infusion of atezolizumab 3 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
干预措施: Atezolizumab (Drug)
Dose Escalation Cohort: Atezolizumab 10 mg/kg
Participants will receive IV infusion of atezolizumab 10 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
干预措施: Atezolizumab (Drug)
Dose Escalation Cohort: Atezolizumab 20 mg/kg
Participants will receive IV infusion of atezolizumab 20 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
干预措施: Atezolizumab (Drug)
Expansion Cohort (Atezolizumab)
Participants will receive IV infusion of atezolizumab q3w up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. The dose which result in total drug exposure less than or equal to (</=) exposures achieved at the MTD or maximum administered dose (MAD), will be selected for expansion cohort.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Atezolizumab
时间窗: Day 1 up to Day 21
Percentage of Participants With Adverse Events
时间窗: Baseline up to 90 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately [approx] 7 years [yrs])
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Day 1 up to Day 21
Recommended Phase 2 Dose (RP2D) of Atezolizumab
时间窗: Baseline up to time of determination of MTD (up to Day 21)
次要结局
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)(Predose(0 hour[hr])on Day 1 of Cycles 1,2,4,8,16,17,20(Cycle length=21 days), every 8 cycles thereafter, at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure(up to approx 7 yrs))
- Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]), Assessed by RECIST v1.1(From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs))
- Percentage of Participants With Objective Response (CR or PR), Assessed by irRC(From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs))
- Duration of Objective Response, Assessed by RECIST v1.1(Time from the first occurrence of a documented objective response to the time of relapse or death from any cause (up to approx 7 yrs))
- Percentage of Participants With Best Overall Response, Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)(From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs))
- Percentage of Participants With Best Overall Response, Assessed by Immune-Related Response Criteria (irRC)(From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs))
- Area Under the Concentration-Time Curve (AUC) of Atezolizumab(Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description))
- Maximum Serum Concentration (Cmax) of Atezolizumab(Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description))
- Minimum Serum Concentration (Cmin) of Atezolizumab(Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description))
- Clearance (CL) of Atezolizumab(Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description))
- Volume at Steady State (Vss) of Atezolizumab(Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description))
- Duration of Objective Response, Assessed by irRC(Time from the first occurrence of a documented objective response to the time of relapse or death from any cause (up to approx 7 yrs))
- Progression-Free Survival (PFS), Assessed by RECIST v1.1(From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs))
- PFS, Assessed by irRC(From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs))