A Phase 1, Open-label, Dose Escalation Study of MGA271 in Pediatric Patients With B7-H3-Expressing Relapsed or Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 25
- 试验地点
- 6
- 主要终点
- Safety and tolerability of enoblituzumab.
研究概览
简要总结
This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or refractory malignant solid tumors.
详细描述
This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or refractory malignant solid tumors.
The study consists of a Dose Escalation Phase to determine the MTD (or MAD) of enoblituzumab followed by a Cohort Expansion Phase to further define the safety and initial antitumor activity of enoblituzumab. In the cohort expansion phase, 5 cohorts of 10 patients each will be enrolled to further evaluate the safety and potential efficacy of enoblituzumab administered at the MTD/MAD in patients with:1) neuroblastoma - measurable disease, 2) neuroblastoma - non-measurable disease, 3) rhabdomyosarcoma, 4) osteosarcoma, and 5) Ewing's sarcoma, Wilms' tumor, desmoplastic small round cell tumors, or malignant solid tumors of any other histology that test positive for B7-H3.
All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC). Disease assessment in patients with neuroblastoma will use neuroblastoma overall response criteria.
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
- 1 Year 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at treatment 1 to 35 years.
- •Relapsed or refractory malignant solid tumors of any histology for which no standard curative therapy is available (escalation phase).
- •Histologically proven: neuroblastoma, rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma/ primitive neuroectodermal tumor, Wilms tumor, desmoplastic small round cell tumor or malignant solid tumors of any other histology that test positive for B7-H3 .
- •Must have malignant solid tumors that demonstrate B7-H3 expression at 2+ or greater levels on the membranous surface of at least 10% of tumor cells or ≥ 25% of tumor vasculature by IHC.
- •With the exception of patients with non-measurable neuroblastoma patients must have measurable disease as per RECIST 1.1
- •Karnofsky (patients ≥ 16 years)/Lansky (patients < 16 years) index ≥
- •Acceptable laboratory parameters and adequate organ reserve.
排除标准
- •Patients are to be excluded from the study if they have any of the following:
- •Patients with a history of symptomatic central nervous system (CNS) unless they have been treated and are asymptomatic.
- •Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment within the past 2 years, and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing.
- •History of prior allogeneic bone marrow/stem-cell or solid organ transplantation.
- •Patients receiving autologous stem cell transplantation must wait 8 weeks before initiation of study drug administration.
- •Treatment with systemic chemotherapy or investigational therapy within 4 weeks of first study drug administration; other agents (e.g., biologics) within 2 weeks; radiation within 2 weeks; patients receiving 131I-MIBG therapy must wait 6 weeks prior to the initiation of study drug administration; corticosteroids (≥ 0.2 mg/kg/day prednisone or equivalent) or other immune suppressive drugs within the 2 weeks prior to the initiation of study drug administration.
- •History of clinically significant cardiovascular disease
- •Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug.
- •Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
- •Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction.
- •Second primary invasive malignancy that has not been in remission for greater than 2 years.
- •History of severe trauma or major surgery within 4 weeks prior to the initiation of study drug administration.
- •Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for enoblituzumab
- •Patients in Canada may not have a history or evidence of latent or active tuberculosis infection.
研究组 & 干预措施
Dose Escalation & Cohort Expansion
enoblituzumab administered IV weekly
干预措施: Enoblituzumab (Drug)
结局指标
主要结局
Safety and tolerability of enoblituzumab.
时间窗: Time of first dose through end of treatment (up to 2 years)
Adverse events, SAEs, incidence of treatment-emergent AE
次要结局
- Peak plasma concentration(Time of first dose through end of treatment (up to 96 weeks))
- Number of participants that develop anti-drug antibodies(Time of first dose through end of treatment (up to 96 weeks))
- Antitumor activity of enoblituzumab(Time of first dose through end of treatment (up to 96 weeks))