A Phase 2 Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 66
- 试验地点
- 56
- 主要终点
- Objective Response Rate (ORR) per Lugano Classification Criteria as Assessed by Investigator
研究概览
简要总结
The primary purpose of the study is to assess the pharmacokinetics (PK) profile of pembrolizumab following subcutaneous (SC) injection of pembrolizumab coformulated with hyaluronidase, and to evaluate the objective response rate (ORR) of pembrolizumab (+) berahyaluronidase alfa SC in adult participants with Relapsed or Refractory Classical Hodgkin Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL). There is no formal hypothesis to be tested for this study.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion criteria include but are not limited to the following:
- •Histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) or primary mediastinal B-cell lymphoma (PMBCL)
- •Radiographically measurable cHL or PMBCL disease assessed by investigator as per Lugano classification
- •Have a life expectancy of >3 months
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
- •Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before enrollment
- •Participants with history of hepatitis C virus (HCV) infection are eligible if they have completed curative antiviral therapy at least 4 weeks before enrollment and HCV viral load is undetectable at screening
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before or on the day of the first dose of study intervention
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has clinically significant (i.e., active) cardiovascular disease
- •Has pericardial effusion or clinically significant pleural effusion
- •Has known additional malignancy that is progressing or has required active treatment within the past 2 years
- •Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- •Received prior monoclonal antibody within 4 weeks prior to first dose of study intervention or has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier
- •Received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
- •Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
- •Received a live or live-attenuated vaccine within 30 days before first dose of study intervention
- •Is receiving systemic antineoplastic chemotherapy, immunotherapy, or biological therapy not specified in this protocol
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Active autoimmune disease that has required systemic treatment in the past 2 years
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Active infection requiring systemic therapy except certain protocol-specified therapies
- •Concurrent active hepatitis B and hepatitis C virus infection
- •Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplant (SCT) within the last 5 years
研究组 & 干预措施
Pembrolizumab Coformulated With Hyaluronidase
Participants with rrCHL and rrPMBCL receive pembrolizumab coformulated with hyaluronidase subcutaneous (SC) injection on Day 1 of each 6-week cycle (Q6W) for up to 18 cycles (approximately 2 years) until documented disease progression per investigator assessment.
干预措施: Pembrolizumab (+) Berahyaluronidase alfa (Biological)
结局指标
主要结局
Objective Response Rate (ORR) per Lugano Classification Criteria as Assessed by Investigator
时间窗: Up to approximately 48 months
ORR is defined as the percentage of the participants who had complete response (CR) or partial response (PR) and will be evaluated using computed tomography (CT) and positron emission tomography (PET)-CT. Response was assessed based on the International Working Group Criteria: Lugano Classification (Cheson et al, Journal of Clinical Oncology, 2014). CR is complete metabolic (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). The percentage of participants who experience CR or PR as assessed by investigator will be presented.
Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase
时间窗: At designated time points (up to ~6 weeks)
Blood samples will be collected at designated timepoints for the determination of Cmax. Cmax is defined as the peak concentration of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase.
Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase
时间窗: At designated time points (up to ~6 weeks)
Blood samples will be collected at designated timepoints for the determination of Ctrough. Ctrough is defined as the lowest concentration of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase.
Area Under the Concentration-Time Curve of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase from Week 0-Week 6 (AUC0-6weeks)
时间窗: At designated time points (up to ~6 weeks)
Blood samples will be collected at designated timepoints for the determination of AUC0-6weeks. AUC0-6 weeks is defined as area under concentration time curve over a 6-week dosing interval of pembrolizumab after administration of SC pembrolizumab coformulated with hyaluronidase.
次要结局
- Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE)(Up to approximately 2 years)
- Duration of Response (DOR) per Lugano Classification Criteria as Assessed by Investigator(Up to approximately 48 months)
- Number of Participants with Antidrug Antibodies (ADA) Level of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase(At designated timepoints (Up to approximately 27 months))
- Maximum Concentration (Cmax) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady-State(At designated time points (up to ~6 weeks))
- Lowest Plasma Concentration (Ctrough) of Pembrolizumab After Administration of SC Pembrolizumab Coformulated with Hyaluronidase at Steady-State(At designated time points (up to ~6 weeks))
- Area Under the Concentration-Time Curve of Pembrolizumab After Administration of SC Pembrolizumab coformulated with Hyaluronidase from Week 0-Week 6 (AUC0-6weeks) at Steady-State(At designated time points (up to ~6 weeks))
- Number of Participants Experiencing an Adverse Event (AE)(Up to approximately 30 months)