A Safety and Pharmacokinetic Study of Single Agent REGN2810 in Pediatric Patients With Relapsed or Refractory Solid or Central Nervous System (CNS) Tumors and a Safety and Efficacy Trial of REGN2810 in Combination With Radiotherapy in Pediatric Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma, Newly Diagnosed High-Grade Glioma, or Recurrent High-Grade Glioma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 57
- 试验地点
- 20
- 主要终点
- Number of Participants Who Developed DLTs (Efficacy Phase)
研究概览
简要总结
Phase 1:
- To confirm the safety and anticipated recommended phase 2 dose (RP2D) of REGN2810 (cemiplimab) for children with recurrent or refractory solid or Central Nervous System (CNS) tumors
- To characterize the pharmacokinetics (PK) of REGN2810 given in children with recurrent or refractory solid or CNS tumors
Phase 2 (Efficacy Phase):
- To confirm the safety and anticipated RP2D of REGN2810 to be given concomitantly with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG)
- To confirm the safety and anticipated RP2D of REGN2810 given concomitantly with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed high-grade glioma (HGG)
- To confirm the safety and anticipated RP2D of REGN2810 given concomitantly with re-irradiation in patients with recurrent HGG
- To assess PK of REGN2810 in pediatric patients with newly diagnosed DIPG, newly diagnosed HGG, or recurrent HGG when given in combination with radiation
- To assess anti-tumor activity of REGN2810 in combination with radiation in improving overall survival at 12 months (OS12) among patients with newly diagnosed DIPG
- To assess anti-tumor activity of REGN2810 in combination with radiation in improving progression-free survival at 12 months (PFS12) among patients with newly diagnosed HGG
- To assess anti-tumor activity of REGN2810 in combination with radiation in improving overall survival at OS12 among patients with recurrent HGG
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
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 0 to <18 years of age (Phase 1)
- •Age ≥3 and ≤25 years of age (Efficacy Phase)
- •Karnofsky performance status ≥50 (patients >16 years) or Lansky performance status ≥50 (patients ≤ 16 years)
- •Life expectancy >8 weeks
- •Adequate Bone Marrow Function
- •Adequate Renal Function
- •Adequate Liver Function
- •Adequate Neurologic Function
排除标准
- •Patients with bulky metastatic disease of the CNS causing Uncal herniation or symptomatic midline shift, significant, symptomatic mass effect, or uncontrolled neurological symptoms such as seizures or altered mental status
- •Patients with metastatic spine disease and gliomatosis as documented by diffuse involvement of >2 lobes
- •Patients who are receiving any other investigational anticancer agent(s)
- •Patients on greater than dexamethasone 0.1 mg/kg/day (maximum 4 mg/day) or equivalent dose in alternate corticosteroid, or actively undergoing corticosteroid dose escalation in the last 7 days
- •Patients with a history of allogeneic stem cell transplant
- •Prior treatment with an agent that blocks the PD-1/PD-L1/PD-L2 pathway
- •Note: Other protocol-defined Inclusion/Exclusion criteria apply
研究组 & 干预措施
Phase 1
Patients in both the Solid Tumor Cohort and the CNS Cohort will receive cemiplimab monotherapy. Each Cohort will have 2 subgroups by age (0 to <12 years, 12 to <18 years).
干预措施: cemiplimab (monotherapy) (Drug)
Efficacy with Newly Diagnosed DIPG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
干预措施: cemiplimab (maintenance) (Drug)
Efficacy with Newly Diagnosed DIPG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
干预措施: Conventional or hypofractionated (Radiation)
Efficacy with Newly Diagnosed HGG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
干预措施: cemiplimab (maintenance) (Drug)
Efficacy with Newly Diagnosed HGG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
干预措施: Conventional or hypofractionated (Radiation)
Efficacy with Recurrent HGG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
干预措施: cemiplimab (maintenance) (Drug)
Efficacy with Recurrent HGG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
干预措施: Re-irradiation (Radiation)
结局指标
主要结局
Number of Participants Who Developed DLTs (Efficacy Phase)
时间窗: Up to 4 weeks post radiation therapy
Number of Treatment-emergent Adverse Events (TEAEs)
时间窗: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
TEAEs are AEs that developed or worsened during the on-treatment period and any treatment-related AEs that occur during the post-treatment period but prior to initiation of other anticancer therapy. Number of TEAEs reported.
Number of Severe (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Grade 3/4/5) TEAEs
时间窗: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
NCI CTCAE version 4.0 was utilized for AE grading of severity: Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE). Number of NCI grade 3/4/5 Treatment-Emergent Adverse Events (AEs) reported
Number of Treatment-emergent Sponsor Identified Immune-related Adverse Events (irAEs)
时间窗: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
Number of sponsor-identified irAEs (all grades) reported.
Number of Severe (NCI CTCAE Grade 3/4/5) Treatment-emergent Sponsor Identified irAEs
时间窗: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
Number of severe treatment-emergent sponsor-identified irAEs reported.
Number of Treatment-emergent AEs of Special Interest (AESI)
时间窗: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
AEs of special interest (AESI) are AEs required to be monitored, documented, and managed in a pre-specified manner as described in the protocol. Number of treatment-emergent AESI reported.
Number of NCI Grade 3/4/5 Treatment-emergent AESI
时间窗: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
Number of NCI grade 3/4/5 treatment-emergent AESI reported
Number of Participants With Any TEAE Resulting in Death
时间窗: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
Number of participants with any TEAE resulting in death reported
Number of Participants With at Least One Lab Abnormality (NCI-CTCAE All Grades) in Hematology, Electrolytes, Liver, Chemistry
时间窗: Up to 36 months
Number of participants with new or worsened laboratory abnormalities (NCI-CTCAE All Grades) reported in Hematology, Electrolytes, Liver, Chemistry; Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE).
Number of Participants Who Developed Dose Limiting Toxicities (DLTs) (Phase 1)
时间窗: Baseline to 28 days
Number of participants who developed dose limiting toxicities (DLTs) in phase 1 reported
Elimination Half-life (t1/2) of Functional Cemiplimab (REGN2810) in Serum
时间窗: Up to 24 months
Trough Concentration (Ctrough) of Functional Cemiplimab (REGN2810) in Serum
时间窗: Up to Week 16
Ctrough (trough concentration) of functional cemiplimab in serum reported.
Peak Concentration (Cmax) of Functional Cemiplimab (REGN2810) in Serum
时间窗: Up to Week 16
Cmax (peak concentration) of functional cemiplimab in serum reported.
Area Under the Concentration-time Curve (AUC) of Functional Cemiplimab (REGN2810) in Serum
时间窗: Up to 24 months
Percentage of Progression-free Survival (PFS) at 12 Months for Participants With Newly Diagnosed HGG (ndHGG)
时间窗: At 12 months
PFS was defined as the time from randomization to the date of the first documented tumor progression, as determined per Response Assessment in Neuro-Oncology (RANO)/Immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria, or death due to any cause.
Percentage of Overall Survival (OS) at 12 Months for Participants With ndDIPG and Recurrent HGG (rHGG)
时间窗: Up to 12 months
OS was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last date that participant was documented to be alive. 95% CI is based on Kaplan-Meier method.
次要结局
- Objective Response Rate (ORR) for Participants Who Have a Confirmed Complete Response (CR) or Partial Response (PR)(Approximately 24 months)
- Number of Participants With Anti-REGN2810 Antibodies (ADA)(1st follow-up visit, approximately 25 months)