A Study of Zilovertamab Vedotin (MK-2140) in Combination With Cyclophosphamide, Doxorubicin, and Prednisone Plus Rituximab or Rituximab Biosimilar (Truxima) (R-CHP) in Participants With Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-007)
- Conditions
- Lymphoma, Large B-Cell, Diffuse (DLBCL)
- Interventions
- Registration Number
- NCT05406401
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study consists of a dose escalation/confirmation phase and an efficacy expansion phase. The dose escalation/confirmation phase is to determine the safety and tolerability and establish a preliminary recommended Phase 2 dose (RP2D) of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease. The efficacy expansion phase is to determine the efficacy of the RP2D of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation Prednisone Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation Rituximab Biosimilar Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Efficacy Expansion Rituximab Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Efficacy Expansion Rituximab Biosimilar Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation Cyclophosphamide Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation Doxorubicin Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation Rituximab Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation Prednisolone Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Efficacy Expansion Cyclophosphamide Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Efficacy Expansion Doxorubicin Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Efficacy Expansion Prednisone Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Efficacy Expansion Prednisolone Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation Zilovertamab Vedotin Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months). Zilovertamab Vedotin + R-CHP: Efficacy Expansion Zilovertamab Vedotin Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months).
- Primary Outcome Measures
Name Time Method Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) in Cycle 1 Cycle 1 (up to 21 days) DLTs will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and are defined as any drug-related adverse event (AE) observed during the DLT evaluation period (e.g. Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle. The number of participants with DLTs in Cycle 1 will be reported.
Number of Participants Who Experienced At Least One AE Up to approximately 8 months An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to approximately 5.5 months An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
Complete Response Rate (CRR) per Lugano Response Criteria Up to approximately 60 months CRR is defined as the percentage of participants who achieve a Complete Response (CR) per Lugano response criteria \[Cheson, B. D., et al 2014\] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with computed tomography (CT) or magnetic resonance imaging (MRI), metabolic imaging with positron emission tomography (PET), and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with CRR will be reported.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) per Lugano Response Criteria Up to approximately 60 months ORR is defined as the percentage of participants who achieve a CR or PR per Lugano response criteria \[Cheson, B. D., et al 2014\] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with CT or MRI, metabolic imaging with PET, and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with ORR will be reported.
Duration of Response (DOR) per Lugano Response Criteria Up to approximately 60 months For participants who demonstrate a confirmed CR or PR per Lugano response criteria \[Cheson, B. D., et al 2014\] for malignant lymphoma, 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. CR and PR assessment includes anatomic imaging with CT or MRI, metabolic imaging with PET, and clinical findings including physical examination and bone marrow biopsy results. DOR as assessed by the investigator will be reported.
Trial Locations
- Locations (22)
Seoul National University Hospital ( Site 0201)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 0200)
🇰🇷Seoul, Korea, Republic of
BC Cancer Victoria-Clinical Trials Unit ( Site 0105)
🇨🇦Victoria, British Columbia, Canada
William Osler Health System ( Site 0106)
🇨🇦Toronto, Ontario, Canada
Hopital du Sacre-Coeur de Montreal ( Site 0108)
🇨🇦Montreal, Quebec, Canada
Hadassah Medical Center ( Site 0401)
🇮🇱Jerusalem, Israel
Sheba Medical Center-Hemato Oncology ( Site 0400)
🇮🇱Ramat Gan, Israel
Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 0306)
🇮🇹Roma, Lazio, Italy
Ospedale San Raffaele-Unità Linfomi ( Site 0305)
🇮🇹Milano, Lombardia, Italy
Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0307)
🇮🇹Palermo, Sicilia, Italy
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant
🇮🇹Alessandria, Italy
Azienda Ospedaliera Universitaria Careggi-SOD Ematologia ( Site 0308)
🇮🇹Firenze, Toscana, Italy
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumat-Oddiał Hematologii Ogólnej ( Site 0503)
🇵🇱Łódź, Lodzkie, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site
🇵🇱Warszawa, Mazowieckie, Poland
Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0504)
🇵🇱Gdańsk, Pomorskie, Poland
Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0505)
🇵🇱Gliwice, Slaskie, Poland
HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Hematology ( Site 0704)
🇪🇸Sevilla, Andalucia, Spain
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 0703)
🇪🇸L'Hospitalet Del Llobregat, Barcelona, Spain
Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 0700)
🇪🇸Madrid, Spain
Mega Medipol-Hematology ( Site 0808)
🇹🇷Stanbul, Istanbul, Turkey
Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 0801)
🇹🇷Ankara, Turkey
Trakya University ( Site 0805)
🇹🇷Edirne, Turkey