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A Clinical Trial of MK-1045 With Zilovertamab Vedotin in Participants With Diffuse Large B-cell Lymphoma (MK-1045-010) (WaveSpan-010)

28 ottobre 2026 aggiornato da: Merck Sharp & Dohme LLC

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

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Stimato)

470

Fase

  • Fase 2
  • Fase 3

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Biologico: MK-1045

Intravenous (IV) administration

Altri nomi:
  • CN201
Biologico: Zilovertamab vedotin

1.5 or 1.75 mg/kg administered IV

Altri nomi:
  • MK-2140
Biologico: Rescue Medication - Biological

Participants may receive Tocilizumab (or biosimilar) after administration of MK-1045 in the event of cytokine release syndrome

Droga: Rescue Medications - Drug

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).

Altro: Granulocyte-colony stimulating factor (G-CSF)

Given as prophylaxis as listed in the National comprehensive Cancer Network guidelines.
Comparatore attivo: 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).
Biologico: Rituximab

375mg/m^2, administered IV

Biologico: Rituximab biosimilar

375 mg/m^2, administered IV

Altri nomi:
  • TRUXIMA®
  • RUXIENCE®
  • RIABNI®
Biologico: Polatuzumab vedotin

1.8 mg/kg, administered IV

Droga: Bendamustine

90 mg/m^2, administered IV for 2 consecutive days

Biologico: Lenalidomide

25 mg, administered orally

Biologico: Tafasitamab

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

Altri nomi:
  • Monjuvi

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Part 1A: Number of Participants Who Experience Dose Limiting Toxicity (DLT)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Part 1A: ORR
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Merck Sharp & Dohme LLC

Investigatori

  • Direttore dello studio: Medical Director, Merck Sharpe & Dohme LLC

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

13 dicembre 2026

Completamento primario (Stimato)

13 marzo 2037

Completamento dello studio (Stimato)

13 marzo 2037

Date di iscrizione allo studio

Primo inviato

28 ottobre 2026

Primo inviato che soddisfa i criteri di controllo qualità

28 ottobre 2026

Primo Inserito (Effettivo)

5 novembre 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

5 novembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

28 ottobre 2026

Ultimo verificato

1 ottobre 2026

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 1045-010
  • 2025 (Sovvenzione/contratto NIH degli Stati Uniti)
  • MK-1045-010 (Altro identificatore: MSD)
  • 2025-524261-24-00 (Identificatore di registro: EU CT)
  • U1111-1330-0209 (Identificatore di registro: UTN)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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