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
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 2 단계
- 3단계
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 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
다른 이름들:
1.5 or 1.75 mg/kg administered IV
다른 이름들:
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. |
|
활성 비교기: 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
다른 이름들:
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
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Part 1A: Number of Participants Who Experience Dose Limiting Toxicity (DLT)
기간: 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)
기간: 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
기간: 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)
기간: 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)
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Part 1A: ORR
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
|
공동 작업자 및 조사자
수사관
- 연구 책임자: Medical Director, Merck Sharpe & Dohme LLC
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 신생물
- 면역계 질환
- 조직학적 유형에 따른 신생물
- 림프계 질환
- 림프 증식 장애
- 면역증식성 장애
- 림프종, 비호지킨
- 림프종, B세포
- 림프종
- 헴 및 림프병
- 림프종, 대형 B세포, 미만성
- 펩타이드
- 아미노산, 펩티드 및 단백질
- 단백질
- 유기 화학 물질
- 이종 사이 클릭 화합물, 1- 링
- 이종 사이 클릭 화합물
- Benzimidazoles
- 이종 사이 클릭 화합물, 2- 링
- 이종 사이 클릭 화합물, 융합 링
- 탄화수소
- 생물학적 요인
- 탄수화물
- 산, acyclic
- 카르 복실 산
- 파이퍼 리딘
- 항체, 모노클로 날
- 항체
- 면역 글로불린
- 면역 단백질
- 혈액 단백질
- 혈청 글로불린
- 글로불린
- 질소 머스타드 화합물
- 겨자 화합물
- 탄화수소, 할로겐화
- 세포 간 신호 전달 펩티드 및 단백질
- 당 단백질
- Glycoconjugates
- 부티레이트
- 항체, 모노클로 날, 뮤린 유래
- 프탈리 미드
- 프탈산
- 산, 카르 보 사이 클릭
- 파이퍼리돈
- Isoindoles
- 식민지 자극 요인
- 조혈 세포 성장 인자
- 사이토 카인
- 레날리도마이드
- 벤다무스틴 염산염
- 리툭시맙
- 폴라투 주맙 베도틴
- 육아 세포 콜로니 자극 인자
- 타파 시타 맙
기타 연구 ID 번호
- 1045-010
- 2025 (미국 NIH 보조금/계약)
- MK-1045-010 (기타 식별자: MSD)
- 2025-524261-24-00 (레지스트리 식별자: EU CT)
- U1111-1330-0209 (레지스트리 식별자: UTN)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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