A Phase 1/Phase 2 Clinical Study to Evaluate the Safety and Efficacy of a Combination of MK-4280 and Pembrolizumab (MK-3475) in Participants With Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 137
- 试验地点
- 25
- 主要终点
- Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
研究概览
简要总结
This study will evaluate the safety and efficacy of favezelimab (MK-4280) in combination with pembrolizumab (MK-3475) using a non-randomized study design in participants with the following hematological malignancies:
- classical Hodgkin lymphoma (cHL)
- diffuse large B-cell lymphoma (DLBCL)
- indolent non-Hodgkin lymphoma (iNHL)
This study will also evaluate the safety and efficacy of pembrolizumab or favezelimab administered as monotherapy in participants with cHL using a 1:1 randomized study design.
The study will have 2 phases: a safety lead-in and an efficacy expansion phase. The recommended Phase 2 dose (RP2D) will be determined in the safety lead-in phase by evaluating dose-limiting toxicities.
There is no primary hypothesis for this study.
详细描述
Per protocol amendment 7, the secondary serum concentration endpoints were removed and will not be reported.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Participants in Part B: Randomized cHL-Monotherapy arm in the study will be randomized (1:1 ratio) to receive pembrolizumab or favezelimab.
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
- •Has measurable disease, defined as ≥1 lesion that can be accurately measured in 2 dimensions with diagnostic quality cross sectional anatomic imaging (computed tomography or magnetic resonance imaging). Minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis
- •Is able to provide a core or excisional tumor biopsy for biomarker analysis from an archival (within 3 months) or newly obtained biopsy at screening
- •Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
排除标准
- •Has known clinically active central nervous system (CNS) involvement
- •Has received prior therapy with an anti-lymphocyte activation gene-3 (LAG-3) antibody
- •Has received chimeric antigen receptors (CAR)-T-cell therapy for cHL and DLBCL Cohorts
- •Has received prior anticancer therapy or thoracic radiation therapy within 14 days before the first dose of study treatment
- •Has ≥Grade 2 non-hematological residual toxicities from prior therapy
- •Has had a prior anticancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to agents administered ≥4 weeks earlier
- •Has received a live vaccine within 30 days prior to first dose of study treatment. Administration of killed vaccines are allowed
- •Has received an investigational agent or used an investigational device within 4 weeks prior to intervention administration
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
- •Has a known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- •Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- •Has an active infection requiring intravenous systemic therapy
- •Has a known history of human immunodeficiency virus (HIV) infection
- •Has known, active hepatitis B or hepatitis C infection
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
- •Has had an allogeneic hematopoetic stem cell/solid organ transplantation within the last 5 years
研究组 & 干预措施
Part A: Favezelimab Dose C+Pembrolizumab
Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose C by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: pembrolizumab (Biological)
Part A: Favezelimab Dose C+Pembrolizumab
Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose C by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: Favezelimab (Biological)
Part B: cHL-Combination Therapy
Participants with cHL receive 200 mg pembrolizumab by IV infusion followed by the recommended Phase 2 dose (RP2D) of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: pembrolizumab (Biological)
Part B: DLBCL-Combination Therapy
Participants with DLBCL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: Favezelimab (Biological)
Part B: iNHL-Combination Therapy
Participants with iNHL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: pembrolizumab (Biological)
Part B: iNHL-Combination Therapy
Participants with iNHL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: Favezelimab (Biological)
Part B: Randomized cHL-Monotherapy
Participants with cHL receive either pembrolizumab by IV infusion or the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to approximately 2 years).
干预措施: pembrolizumab (Biological)
Part B: Randomized cHL-Monotherapy
Participants with cHL receive either pembrolizumab by IV infusion or the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles (up to approximately 2 years).
干预措施: Favezelimab (Biological)
Part A: Favezelimab Dose A+pembrolizumab
Participants receive 200 mg pembrolizumab by intravenous (IV) infusion followed by favezelimab Dose A by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: pembrolizumab (Biological)
Part A: Favezelimab Dose B+pembrolizumab
Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose B by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: Favezelimab (Biological)
Part B: cHL-Combination Therapy
Participants with cHL receive 200 mg pembrolizumab by IV infusion followed by the recommended Phase 2 dose (RP2D) of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: Favezelimab (Biological)
Part A: Favezelimab Dose A+pembrolizumab
Participants receive 200 mg pembrolizumab by intravenous (IV) infusion followed by favezelimab Dose A by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: Favezelimab (Biological)
Part A: Favezelimab Dose B+pembrolizumab
Participants receive 200 mg pembrolizumab by IV infusion followed by favezelimab Dose B by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: pembrolizumab (Biological)
Part B: DLBCL-Combination Therapy
Participants with DLBCL receive 200 mg pembrolizumab by IV infusion followed by the RP2D of favezelimab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles (up to approximately 2 years).
干预措施: pembrolizumab (Biological)
结局指标
主要结局
Percentage of Participants Experiencing a Dose-limiting Toxicity (DLT)
时间窗: Cycle 1 (up to 21 days)
DLT will be defined as any drug-related adverse event (AE) observed during the DLT evaluation period (Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle and reported as the percentage of participants experiencing a DLT defined by the National Cancer Institute Common Terminology for Adverse Events version 4.0.
Percentage of Participants with Treatment Discontinuations Due to an AE
时间窗: From time of signing informed consent form (ICF) until the end of study treatment (up to approximately 24 months)
Percentage of participants discontinuing study treatment due to an AE
Percentage of Participants Experiencing an Adverse Event (AE)
时间窗: From time of signing informed consent form (ICF) until the end of follow-up (up to approximately 27 months)
Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment
次要结局
- Objective Response Rate (ORR)(Up to approximately 24 months)