An Early-Phase, Multicenter, Open-Label Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) In Pediatric and Young Adult Patients With Previously Treated Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 87
- 试验地点
- 30
- 主要终点
- Minimum Serum Concentration (Cmin) of Atezolizumab
研究概览
简要总结
This early phase, multicenter, open-label, single-arm study evaluated the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of atezolizumab in pediatric and young adult participants with solid tumors for which prior treatment was proven to be ineffective.
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
- — 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric solid tumor (including Hodgkin's and Non-Hodgkin's lymphoma), for which prior treatment had proven to be ineffective (that is, relapsed or refractory) or intolerable
- •Disease that is measurable as defined by RECIST v1.1, mINRC, Revised Response Criteria for Malignant Lymphoma, RANO criteria (as appropriate) or evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers, or other reliable measures
- •Archival tumor tissue block or 15 freshly cut, unstained, serial slides available for submission, or willingness to undergo a core or excisional biopsy prior to enrollment (fine-needle aspiration, brush biopsy, and lavage samples are not acceptable).
- •Participants with fewer than 15 slides available may be eligible for study entry following discussion with Medical Monitor
- •Lansky Performance Status (participants less than [<] 16 years old) or Karnofsky Performance Status (participants greater than or equal to [>=] 16 years old) >=50
- •Life expectancy >=3 months, in the investigator's judgment
- •Adequate hematologic and end organ function, confirmed by laboratory results obtained within 28 days prior to initiation of study drug
排除标准
- •Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases, except ATRT
- •Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
- •Prior allogeneic hematopoietic stem-cell transplantation or prior solid-organ transplantation
- •Treatment with chemotherapy (other than high-dose chemotherapy as described above) or differentiation therapy (such as retinoic acid) or immunotherapy (such as anti-GD2 antibody treatment) within 3 weeks prior to initiation of study drug or, if treatment included nitrosoureas, within 6 weeks prior to initiation of study drug
- •Treatment with thoracic or mediastinal radiotherapy within 3 weeks prior to initiation of study drug
- •Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives) or biologic therapy within 4 weeks or 5 half-lives, whichever is shorter, prior to initiation of study drug. This requirement may be waived at the investigator's request if the participant has recovered from therapeutic toxicity to the degree specified in the protocol, with approval of the Medical Monitor
- •Treatment with a long-acting hematopoietic growth factor within 2 weeks prior to initiation of study drug or a short-acting hematopoietic growth factor within 1 week prior to initiation of study drug
- •Treatment with investigational therapy (with the exception of cancer therapies as described above) within 4 weeks prior to initiation of study drug
- •Treatment with a live vaccine or a live, attenuated vaccine (e.g., nasal spray of live attenuated influenza vaccine or FluMist®) within 4 weeks prior to initiation of study drug or anticipation that such treatment will be required during the study or within 5 months after the final dose of study drug
- •Treatment with herbal cancer therapy within 1 week prior to initiation of study drug
- •Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibodies
- •Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin 2 [IL-2]) within 6 weeks or five drug elimination half-lives prior to Day 1 of Cycle 1, whichever is longer
- •Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) at the time of initiation of study drug, or anticipated requirement for systemic immunosuppressive medications during the study
- •Current treatment with therapeutic anticoagulants
- •Any non-hematologic toxicity (excluding alopecia) from prior treatment that has not resolved to Grade less than or equal to (<=) 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) at screening
- •Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
研究组 & 干预措施
Atezolizumab
Participants received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams [mg]) on Day 1 of each 21-day cycle.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Minimum Serum Concentration (Cmin) of Atezolizumab
时间窗: PRD (0 hr) on D1 of Cy2,3,4,8, 12, 16 (1 Cy=21 days) and every 8 cycles thereafter; at any time during visit at study drug discontinuation visit, at least 90 days (maximum 150 days) after the last dose of study drug (up to approximately 42 months)
Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma
时间窗: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors
时间窗: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants With Solid Tumors
时间窗: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Note: In Cohort 5, the response was observed in a rhabdoid tumor. Participant was erroneously enrolled in the Non-rhabdomyosarcoma soft tissue sarcoma cohort.
PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma
时间窗: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
时间窗: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest
时间窗: From baseline up to approximately 42 months
Maximum Serum Concentration (Cmax) of Atezolizumab
时间窗: Predose (PRD; 0 hours [hr]), 0.5 hr post-infusion (P-I; infusion duration=30-60 minutes) on Day (D) 1 of Cycle (Cy) 1 and 4 (1 Cy=21 days)
Atezolizumab Serum Concentration at Washout
时间窗: At least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
Area Under the Concentration-Time Curve (AUC) of Atezolizumab
时间窗: PRD (0 hr), 0.5 hr P-I (infusion duration=30-60 minutes) on D1 of Cy1; at any time during visit on Cy1D8 (1 Cy=21 days)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
时间窗: PRD (0 hr) on D1 of Cy1,2,3,4,8,12,16 (1 Cy=21 days) & every 8 cycles thereafter; at any time during visit on Cy1D8, study drug discontinuation, at least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT
时间窗: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) in Participants With Neuroblastoma
时间窗: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
时间窗: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Response Assessment in Neuro-Oncology (RANO) Criteria in Participants With Atypical Teratoid Rhabdoid Tumor (ATRT)
时间窗: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
次要结局
- DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- Optimal Dose of Atezolizumab in Pediatric Adult Participants(From baseline up to approximately 42 months)
- Overall Survival (OS)(Baseline until death (up to approximately 42 months))
- Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Related Response Criteria (irRC) for Participants With Neuroblastoma(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- PFS as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- DOR as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))
- Optimal Dose of Atezolizumab in Young Adult Participants(From baseline up to approximately 42 months)
- DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT(Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months))