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
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 3
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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
他の名前：
1.5 or 1.75 mg/kg administered IV
他の名前：
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. |
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アクティブコンパレータ：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
他の名前：
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
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Part 1A: Number of Participants Who Experience Dose Limiting Toxicity (DLT)
時間枠：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)
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Part 1A: ORR
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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)
|
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Part 1A and 1B: Maximum Concentration (Cmax) of MK-1045
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
|
協力者と研究者
スポンサー
捜査官
- スタディディレクター：Medical Director、Merck Sharpe & Dohme LLC
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
- 新生物
- 免疫系疾患
- 組織型別の新生物
- リンパ疾患
- リンパ増殖性疾患
- 免疫増殖性疾患
- リンパ腫、非ホジキン
- リンパ腫、B細胞
- リンパ腫
- ヘミックおよびリンパ疾患
- リンパ腫、大型B細胞、びまん性
- ペプチド
- アミノ酸、ペプチド、およびタンパク質
- タンパク質
- 有機化学物質
- 複素環化化合物、1リング
- 複素環化化合物
- ベンジミダゾール
- 複素環化化合物、2リング
- 複素環化化合物、融合リング
- 炭化水素
- 生物学的要因
- 炭水化物
- 酸、非環式
- カルボン酸
- ピペリジン
- 抗体、モノクローナル
- 抗体
- 免疫グロブリン
- 免疫タンパク質
- 血液タンパク質
- 血清グロブリン
- グロブリン
- 窒素マスタード化合物
- マスタード化合物
- 炭化水素、ハロゲン化
- 細胞間シグナル伝達ペプチドとタンパク質
- 糖タンパク質
- グリココンジュゲート
- 酪酸
- 抗体、モノクローナル、マウス由来
- フタリミド
- フタル酸
- 酸、炭素環
- ピペリドン
- イソインドール
- コロニー刺激因子
- 造血細胞成長因子
- サイトカイン
- レナリドミド
- ベンダムスチン塩酸塩
- リツキシマブ
- ポラツマブヴェドチン
- 顆粒球コロニー刺激因子
- タファシタマブ
その他の研究ID番号
- 1045-010
- 2025 (米国 NIH グラント/契約)
- MK-1045-010 (その他の識別子：MSD)
- 2025-524261-24-00 (レジストリ識別子：EU CT)
- U1111-1330-0209 (レジストリ識別子：UTN)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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