A Clinical Trial of MK-1045 With Zilovertamab Vedotin in Participants With Diffuse Large B-cell Lymphoma (MK-1045-010) (WaveSpan-010)
A Phase 2/3 Multi-arm, Open-label Study of MK-1045 in Combination With Zilovertamab Vedotin in Participants With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Researchers are looking for new ways to treat relapsed or refractory, diffuse large B-cell lymphoma (R/R DLBCL). Relapsed means the cancer came back after treatment. Refractory means the number of cancer cells in the body did not go down or the cancer did not go away after treatment. Researchers want to learn if MK-1045, an immunotherapy, can treat R/R DLBCL when given with zilovertamab vedotin (ZV), a type of targeted therapy.
The goals of this trial are to learn:
- About the safety of MK-1045 and ZV and if participants tolerate them together. To tolerate these drugs together means that participants will receive the trial medicines unless they need to stop them due to health problems
- About the number of participants whose cancer responds (gets smaller or goes away) to treatment with MK-1045 and ZV
- If participants who receive MK-1045 and ZV live longer without the cancer growing or spreading compared to participants who receive standard treatments
研究概览
地位
研究类型
注册 (估计的)
阶段
- 阶段2
- 第三阶段
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Has histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma, not otherwise specified (DLBCL-NOS), by prior biopsy.
- Part 1 participants: Has relapsed or refractory DLBCL after at least 2 prior systemic DLBCL therapies; Part 2 participants: Has relapsed or refractory DLBCL after at least 1 prior systemic DLBCL therapy.
- Is ineligible for or progressed after autologous stem cell transplant (ASCT) or chimeric antigen receptor T-cell (CAR-T) therapy.
- Has locally confirmed cluster of differentiation 19 (CD19) expression in tumor tissue obtained after disease progression on CD19-targeting therapy, if had disease progression after CD19-targeting therapy.
- Has radiographically measurable DLBCL per Lugano response criteria.
- Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
- If human immunodeficiency virus (HIV)-infected, has well-controlled HIV on antiretroviral therapy.
- If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load and received and will continue to receive HBV antiviral therapy.
- If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load.
Exclusion Criteria:
- Has a diagnosis of primary mediastinal B-cell lymphoma.
- Has received a solid organ transplant.
- Has a known or suspected history of hemophagocytic lymphohistiocytosis (HLH).
- Has a rare type of DLBCL.
- Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- Has a history of serious cardiovascular or cerebrovascular diseases.
- Has a demyelinating form of Charcot-Marie-Tooth disease.
- Has ongoing corticosteroid therapy (in dosing exceeding 30 mg daily of prednisone equivalent).
- Has a known additional malignancy that is progressing or required active treatment in the past 3 years.
- Has a history or presence of clinically relevant central nervous system (CNS) diseases.
- Has known active CNS lymphoma or involvement of CNS with DLBCL.
- Has an active autoimmune disease that required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
- Has an active infection requiring systemic therapy.
- Has prior allogeneic stem cell transplantation and has acute graph versus host disease (GVHD), ongoing chronic GVHD, or requires systemic immunosuppression for treatment/prophylaxis of GVHD.
- Has not adequately recovered from surgery or has ongoing surgical complications.
- Has been found to be primary refractory to monomethyl auristatin E (MMAE)-containing agents
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：顺序分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Part 1 and Part 2: MK-1045 plus Zilovertamab vedotin (ZV)
Participants will receive escalating doses (2 to 120mg) of MK-1045 (or in Part 2, a dose of MK-1045 determined by Part 1) via intravenous infusion (IV) once weekly (q1w) for 48 weeks plus 1.5 or 1.75 mg/kg ZV via IV infusion once every 3 weeks (q3w) for 18 weeks. Participants may continue to receive MK-1045 once every 2 weeks (q2w) after 3 months if a Complete Response (CR) is achieved. |
Intravenous (IV) administration
其他名称：
1.5 or 1.75 mg/kg administered IV
其他名称：
Participants may receive Tocilizumab (or biosimilar) after administration of MK-1045 in the event of cytokine release syndrome Participants may receive the following rescue medications before administration of MK-1045: acetaminophen (or similar), diphenhydramine (or similar antihistamine), dexamethasone, Varicellazoster/herpes simplex virus prophylaxis (acyclovir, valacyclovir, famiciclovir), and pneumocystis jirovecii pneumonia prophylaxis (trimethoprim/sulfamethoxazole, dapsone, atovaquone, pentamidine). Given as prophylaxis as listed in the National comprehensive Cancer Network guidelines. |
|
有源比较器：Part 2: Physician's Choice of Chemotherapy
Participants will receive physician's choice of: 12 mg/kg tafasitamab per labeling instructions plus 25mg lenalidomide once daily (qd) from Days 1-21 of each cycle (each cycle is 28 days) for up to 12 cycles followed by 12 mg/kg tafasitamab monotherapy q2w if stable OR 1.8 mg/kg polatuzumab vedotin plus 90 mg/m^2 bendamustine and 375 mg/m^2 rituximab (or biosimilar) q3w for 6 cycles (each cycle is 21 days). |
375mg/m^2, administered IV 375 mg/m^2, administered IV
其他名称：
1.8 mg/kg, administered IV 90 mg/m^2, administered IV for 2 consecutive days 25 mg, administered orally 12 mg/kg, administered IV, on Days 1, 4, 8, 15, and 22 for Cycle 1; Days 1, 8, 15, and 22 for Cycles 2 and 3; Days 1 and 15 for Cycles 4 to 12 (each Cycle is 28 days). After Cycle 12, administered once every 2 weeks
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Part 1A: Number of Participants Who Experience Dose Limiting Toxicity (DLT)
大体时间：Up to approximately 42 days
|
The following events, if considered drug related by the Investigator, will be considered a DLT: Grade (Gr) 5 toxicity; Gr 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia associated with any Gr2 or higher bleeding; Nonhematologic AEs ≥Gr 3 with exceptions; Gr 3 or Gr 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, or persists for >72 hours; Gr 3 of 4 febrile neutropenia; Treatment-related toxicities that lead to discontinuation of study treatment or results in receiving incomplete planned doses of study treatment during DLT evaluation window (up to approximately 42 days). |
Up to approximately 42 days
|
|
Part 1A and 1B: Number of Participants Who Experience an Adverse Event (AE)
大体时间：Up to approximately 53 months
|
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
Up to approximately 53 months
|
|
Part 1A and 1B: Number of Participants Who Discontinue Study Treatment Due to an AE
大体时间：Up to approximately 11 months
|
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
Up to approximately 11 months
|
|
Part 1B: Objective Response Rate (ORR)
大体时间：Up to approximately 53 months
|
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 50% decrease in the sum of diameters of target lesions) per Lugano response criteria. The percentage of participants who experience CR or PR as assessed by physician investigator will be presented. |
Up to approximately 53 months
|
|
Part 2: Progression Free Survival (PFS)
大体时间：Up to approximately 53 months
|
PFS is defined as the time from randomization to the first documented disease progression per Lugano response criteria by Blinded Independent Central Review (BICR) or death due to any cause, whichever occurs first. |
Up to approximately 53 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Part 1A: ORR
大体时间：Up to approximately 53 months
|
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 50% decrease in the sum of diameters of target lesions) per Lugano response criteria. The percentage of participants who experience CR or PR as assessed by physician investigator will be presented. |
Up to approximately 53 months
|
|
Part 1A and 1B: Duration of Response (DOR)
大体时间：Up to approximately 53 months
|
For participants who demonstrate a CR or PR per Lugano response criteria as assessed by physician investigator. DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. |
Up to approximately 53 months
|
|
Part 1A and 1B: Complete Response Rate (CRR)
大体时间：Up to approximately 53 months
|
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) per Lugano response criteria. CR rate is defined as the percentage of participants who experience a CR. The CR rate as assessed by physician investigator will be presented. |
Up to approximately 53 months
|
|
Part 1A and 1B: Area Under the Time Concentration Curve (AUC) of MK-1045
大体时间：Predose and at designated time points post-dose (up to approximately 11 months)
|
Blood samples will be collected at designated timepoints to estimate the AUC of MK-1045. |
Predose and at designated time points post-dose (up to approximately 11 months)
|
|
Part 1A and 1B: Maximum Concentration (Cmax) of MK-1045
大体时间：Predose and at designated time points post-dose (up to approximately 11 months)
|
Blood samples will be collected at designated timepoints to estimate the Cmax of MK-1045. |
Predose and at designated time points post-dose (up to approximately 11 months)
|
|
Part 1A and 1B: Minimum Concentration Just Before the Next Dose (Ctrough) of MK-1045
大体时间：Predose and at designated time points post-dose (up to approximately 11 months)
|
Blood samples will be collected at designated timepoints to estimate the Ctrough of MK-1045. |
Predose and at designated time points post-dose (up to approximately 11 months)
|
|
Part 2: Overall Survival (OS)
大体时间：Up to approximately 53 months
|
OS is defined as the time from randomization to death due to any cause. |
Up to approximately 53 months
|
|
Part 2: ORR
大体时间：Up to approximately 53 months
|
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 50% decrease in the sum of diameters of target lesions) per Lugano response criteria. The percentage of participants who experience CR or PR as assessed by BICR will be presented. |
Up to approximately 53 months
|
|
Part 2: Number of Participants Who Experience an AE
大体时间：Up to approximately 53 months
|
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
Up to approximately 53 months
|
|
Part 2: Number of Participants Who Discontinue Study Treatment Due to an AE
大体时间：Up to approximately 11 months
|
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
Up to approximately 11 months
|
|
Part 2: CRR
大体时间：Up to approximately 53 months
|
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) per Lugano response criteria. CR rate is defined as the percentage of participants who experience a CR. The CR rate as assessed by BICR will be presented. |
Up to approximately 53 months
|
|
Part 2: DOR
大体时间：Up to approximately 53 months
|
For participants who demonstrate a CR or PR per Lugano response criteria as assessed by BICR. DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. |
Up to approximately 53 months
|
|
Part 2: Minimal Residual Disease (MRD) Negativity Rate
大体时间：Predose and at designated time points post-dose (up to approximately 11 months)
|
MRD is defined as the percentage of participants reaching MRD negativity by ctDNA clearance at predefined timepoints. |
Predose and at designated time points post-dose (up to approximately 11 months)
|
合作者和调查者
调查人员
- 研究主任：Medical Director、Merck Sharpe & Dohme LLC
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
- 肿瘤
- 免疫系统疾病
- 组织学类型的肿瘤
- 淋巴系统疾病
- 淋巴增生性疾病
- 免疫增生性疾病
- 淋巴瘤，非霍奇金
- 淋巴瘤，B细胞
- 淋巴瘤
- 半身和淋巴疾病
- 淋巴瘤，大 B 细胞，弥漫性
- 肽
- 氨基酸，肽和蛋白质
- 蛋白质
- 有机化学品
- 杂环化合物，1形
- 杂环化合物
- 苯甲酰唑
- 杂环化合物，2环
- 杂环化合物，融合环
- 碳氢化合物
- 生物因素
- 碳水化合物
- 酸，无环
- 羧酸
- 哌啶
- 抗体，单克隆
- 抗体
- 免疫球蛋白
- 免疫蛋白
- 血蛋白
- 血清球蛋白
- 球蛋白
- 氮芥末化合物
- 芥末化合物
- 碳氢化合物，卤素
- 细胞间信号肽和蛋白质
- 糖蛋白
- 糖缀合物
- 丁酸酯
- 抗体，单克隆，鼠的衍生
- 邻苯二甲胺
- 邻苯二甲酸
- 酸，碳环
- 哌啶酮
- 等词
- 菌落刺激因素
- 造血细胞生长因子
- 细胞因子
- 来那度胺
- 盐酸苯达莫司汀
- 利妥昔单抗
- polatuzumab vedotin
- 粒细胞群刺激因子
- Tafasitamab
其他研究编号
- 1045-010
- 2025 (美国 NIH 拨款/合同)
- MK-1045-010 (其他标识符：MSD)
- 2025-524261-24-00 (注册表标识符：EU CT)
- U1111-1330-0209 (注册表标识符：UTN)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
药物和器械信息、研究文件
研究美国 FDA 监管的药品
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