A Phase 1/2 Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Relatlimab Plus Nivolumab in Pediatric and Young Adult Participants With Recurrent or Refractory Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 122
- 主要终点
- Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, drug levels, and preliminary efficacy of relatlimab plus nivolumab in pediatric and young adult participants with recurrent or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Participants with pathologically confirmed high-risk R/R cHL, after non-response to or failure of 1or more lines of standard therapy.
- •Participants with pathologically confirmed R/R NHL after non-response to or failure of 1or more lines of standard therapy, including, but not limited to, R/R primary mediastinal B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), mediastinal gray zone lymphoma (MGZL), anaplastic large cell lymphoma (ALCL), or peripheral T-cell lymphoma (PTCL).
- •Participants with pathologically confirmed R/R NHL after non-response to or failure of 2 or more lines of standard therapy, including Burkitt lymphoma (blast count <25% malignant Burkitt cells and/or per the investigator's clinical assessment of risk status), lymphoblastic lymphoma (blast count < 25% of marrow nucleated cells and/or per the investigator's clinical assessment of risk status), NK/T-cell lymphoma (nasal and non-nasal NK/T-cell lymphoma subtypes, but not aggressive NK/T-cell leukemia/lymphoma subtype).
- •The participant's current disease state must be R/R to standard therapy.
- •Participants must have measurable PET positive disease in both cHL and NHL cohorts.
排除标准
- •Primary CNS lymphoma of the brain or spinal cord, and secondary CNS lymphoma (ie, from systemic non-Hodgkin lymphoma) involving the brain, spinal cord, or with leptomeningeal seeding.
- •Prior treatment with an anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, with the exception of anti-PD(L)-1 targeted therapies.
- •Prior treatment with lymphocyte activation gene-3 (LAG-3)-targeted agents.
- •Participants with clinically significant systemic illnesses unrelated to the cancer as judged by the investigators, which would compromise the participant's ability to tolerate the study treatment.
- •Participants with autoimmune disease.
- •Prior allogeneic bone marrow transplantation.
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Relatlimab + Nivolumab
干预措施: Relatlimab (Drug)
Relatlimab + Nivolumab
干预措施: Nivolumab (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: Up to 135 days following last dose
DLT evaluation window is 4 weeks from start of treatment. Safety evaluation will continue up to 135 days following last dose.
Maximum tolerated dose or Recommended phase 2 dose (MTD/RP2D)
时间窗: Up to 135 days following last dose
Number of participants with Adverse Events (AEs)
时间窗: Up to 135 days following last dose
Number of participants with serious adverse events (SAEs)
时间窗: Up to 135 days following last dose
Number of participants with AEs leading to discontinuation
时间窗: Up to 135 days following last dose
Number of deaths
时间窗: Up to 2 years from the last treatment of last participant
Number of participants with clinical laboratory abnormalities
时间窗: Up to 135 days following last dose
Maximum observed plasma concentration (Cmax)
时间窗: Up to 96 weeks
Trough observed concentration (Ctrough)
时间窗: Up to 96 weeks
Time of maximum observed plasma concentration (Tmax)
时间窗: Up to 96 weeks
Area Under the Curve within a dosing interval (AUC(TAU))
时间窗: Up to 96 weeks
Complete Metabolic Response (CMR) Rate defined as the proportion of all response-evaluable participants who achieve the best response of CMR using Lugano 2014 criteria
时间窗: Up to 2 years from the last treatment of last participant
Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A
时间窗: 1 cycle, defined as 28 days
Hepatic DLT * ALT or AST \> 8 × ULN * ALT or AST \> 5 and ≤ 8 × ULN, that fails to return to ≤ Grade 1 within 2 weeks despite medical intervention. * TB \> 5 × ULN. * ALT or AST \> 3 × ULN and concurrent total bilirubin \> 2 × ULN. Non-Hematologic DLT * ≥ Grade 2 episcleritis, uveitis, iritis or any other immune-related eye pain or reduction in visual acuity that requires systemic treatment. * ≥ Grade 3 non-hepatic or non-hematologic toxicity with the exceptions noted below. Hematologic DLT * Grade 4 anemia not explained by underlying disease. * Grade 3 febrile neutropenia lasting \> 48 hours, or Grade 4 febrile neutropenia * Grade 4 neutropenia that does not resolve to Grade 3 or less within 5 days of initiation of granulocyte colony stimulating factor. * Grade 3 thrombocytopenia associated with clinically significant bleeding. * Grade 3 hemolysis
Complete Metabolic Response (CMR) Rate - Part B
时间窗: From first dose until the first documented response
The CMR rate is defined as the percentage of all response-evaluable participants who achieve the best response of CMR using Lugano 2014 criteria. No participants enrolled in Part B.
Number of Participants With Adverse Events (AEs) - Part A
时间窗: From first dose to 135 days post last dose (Up to approximately 11 months)
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment.
Number of Participants Who Died - Part A
时间窗: from first dose to 135 days post last dose (Up to approximately 11 months)
Number of participants who died due to any cause
Number of Participants With Serious Adverse Events (SAEs) - Part A
时间窗: from first dose to 135 days post last dose (Up to approximately 11 months)
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization.
Number of Participants With Adverse Events (AEs) Leading to Discontinuation - Part A
时间窗: From first dose to 135 days post last dose (Up to approximately 11 months)
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment.
Number of Participants With Laboratory Abnormalities - Part A
时间窗: From first dose to 30 days post last dose (Up to approximately 8 months)
Number of participants with Grade ≥ 3 laboratory abnormalities in hematology and serum chemistry. Grade 3=severe Grade 4=life-threatening Grade 5=death
Maximum Serum Concentration (Cmax)
时间窗: Cycle 1 Day 1
Maximum observed serum concentration of Analyte BMS-986016
Time to Maximum Concentration (Tmax)
时间窗: Cycle 1 Day 1
Time of maximum observed serum concentration of Analyte BMS-986016
Area Under the Concentration-time Curve [AUC(TAU)]
时间窗: Cycle 1 Day 1
Area Under the Concentration-time Curve \[AUC(TAU)\] for Analyte BMS-986016
Concentration Trough (Ctrough)
时间窗: Cycle 2 Day 1, Cycle 4 Day 1, Cycle 6 Day 1
Concentration Trough (Ctrough) for Analyte BMS-986016 and BMS-936558
次要结局
- Number of participants with AEs(Up to 135 days following last dose)
- Number of participants with SAEs(Up to 135 days following last dose)
- Number of participants with AEs leading to discontinuation(Up to 135 days following last dose)
- Number of deaths(Up to 2 years from the last treatment of last participant)
- Number of participants with clinical laboratory abnormalities(Up to 135 days following last dose)
- Overall Response Rate (ORR) defined as the proportion of all response- evaluable participants who achieve a best response of CMR or partial metabolic response (PMR) using the Lugano 2014 classification(Up to 2 years from the last treatment of last participant)
- Number of Participants With Adverse Events (AEs) - Part B(From first dose to 135 days post last dose)
- Number of Participants With Serious Adverse Events (SAEs) - Part B(From first dose to 135 days post last dose)
- Number of Participants With Adverse Events Leading to Discontinuation - Part B(From first dose to 135 days post last dose)
- Number of Participants Who Died - Part B(From first dose to 135 days post last dose)
- Number of Participants With Laboratory Abnormalities - Part B(From first dose to 135 days post last dose)
- Objective Response Rate (ORR) - Part B(From to)