A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated DLBCL (MK-2140-010)

Phase 3

Not yet recruiting

• Conditions: Diffuse Large B-Cell Lymphoma
• Interventions: Biological: Zilovertamab vedotin; Biological: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Biological: Rituximab Biosimilar; Drug: Prednisone; Drug: Prednisolone; Drug: Vincristine

• Registration Number: NCT06717347
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to evaluate if zilovertamab vedotin with standard treatment can help people live longer without the cancer growing or spreading than people who receive standard treatment alone.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Related News

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-02
• Study First Submitted QC: 2024-12-03
• Last Update Submitted: 2024-12-03
• Study First Posted: 2024-12-05
• Last Update Posted: 2024-12-05
• Study Start: 2024-12-27
• Primary Completion: 2032-03-29
• Study Completion: 2032-03-29

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1046

Inclusion Criteria

• Has histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues.
• Has positron emission tomography (PET) positive disease at screening, defined as 4 to 5 on the Lugano 5-point scale.
• Has received no prior treatment for their DLBCL.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before randomization.
• Has an ejection fraction ≥45% as determined by either echocardiogram (ECHO) or multigated acquisition (MUGA).
• Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART).
• Who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load prior to randomization.
• Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

Read More

Exclusion Criteria

• Has a history of transformation of indolent disease to DLBCL.
• Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL) or Grey zone lymphoma.
• Has Ann Arbor Stage I DLBCL.
• Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication.
• Has clinically significant pericardial or pleural effusion.
• Has ongoing Grade >1 peripheral neuropathy.
• Has a demyelinating form of Charcot-Marie-Tooth disease.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Has ongoing corticosteroid therapy.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Known additional malignancy that is progressing or has required active treatment within the past 2 years.
• Known active central nervous system (CNS) lymphoma.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Has active infection requiring systemic therapy.
• Has concurrent active HBV (defined as HBsAg positive and detectable HBV DNA) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid (RNA)) infection.
• Has history of allogeneic tissue/solid organ transplant.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)	Zilovertamab vedotin	Participants receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)	Rituximab	Participants receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)	Cyclophosphamide	Participants receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)	Doxorubicin	Participants receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)	Rituximab Biosimilar	Participants receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)	Prednisone	Participants receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)	Prednisolone	Participants receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Zilovertamab vedotin	Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Rituximab	Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Cyclophosphamide	Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Doxorubicin	Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Rituximab Biosimilar	Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Prednisone	Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Prednisolone	Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Vincristine	Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Up to ~ 50 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.

Secondary Outcome Measures

Name	Time	Method
Complete Response at End of Treatment (CR at EOT)	Up to ~ 32 months	CR at EOT is defined as a CR per Lugano response criteria as assessed by BICR at end of treatment. Participants with missing data or who discontinue treatment or study prior to reaching EOT will be considered non-responders and included in the total number of participants.
Overall Survival (OS)	Up to ~ 74 months	OS is defined as the time from randomization to death due to any cause.
Event-free Survival (EFS)	Up to ~ 74 months	EFS is defined as the time from randomization to any of the following events: progressive disease that precludes surgery, local or distant recurrence, second primary malignancy or death due to any cause. The EFS for all participants will be presented.
Duration of Complete Response (DurCR)	Up tp ~ 74 months	For participants who demonstrate CR at EOT per Lugano response criteria by BICR, duration of complete response is defined as the time from the first documented evidence of CR at or before EOT until disease progression or death due to any cause, whichever occurs first.
Number of Participants Who Experience an Adverse Event (AE)	Up to approximately 9 months	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.
Number of Participants Who Discontinue Study Treatment Due to an AE	Up to approximately 6 months	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
Change From Baseline in Health-Related Quality Of Life (HRQoL) on Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Trial Outcome Index (TOI)	Baseline and Week 25	The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden w...
Change From Baseline in HRQoL on FACT-Lym Total Score	Baseline and Week 25	The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden w...
Change From Baseline in HRQoL on Physical Wellbeing (PWB) (Items GP1 through GP7)	Baseline and Week 25	The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden w...
Change From Baseline in HRQoL on Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) Neurotoxicity Subscale Score	Baseline and Week 25	The FACT GOG-NTX provides a targeted assessment of symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity. It is an 11-item questionnaire designed to measure the neurotoxicity subscale. The scoring of FACT GOG-NTX is on a 5-point Likert scale from 0 to 4, with 0= not at all, 1= a little bit, 2= somewhat, 3=qui...