A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combin... | NCT06717347

NCT06717347

ID	Type	Description
MK-2140-010	Other Identifier	MSD
2024-515566-13-00	Registry Identifier	EU CT
U1111-1309-3971	Registry Identifier	UTN
jRCT2061240099	Other Identifier	jRCT

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)	Experimental	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) plus 2 cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants also receive 100 mg prednisone, prednisolone, or methylprednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).	Biological: Zilovertamab vedotin Biological: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Biological: Rituximab Biosimilar Drug: Prednisone Drug: Prednisolone Drug: Rescue medication Drug: Methylprednisolone
Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP)	Active Comparator	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) plus 2 cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants also receive 100 mg prednisone, prednisolone, or methylprednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).	Biological: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Biological: Rituximab Biosimilar Drug: Prednisone Drug: Prednisolone Drug: Vincristine Drug: Methylprednisolone

Name	Type	Description	Arm Group Labels	Other Names
Zilovertamab vedotin	Biological	IV infusion	Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free survival (PFS)	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 ~ 50 months

Secondary Outcomes

Measure	Description	Time Frame
Complete Response at End of Treatment (CR at EOT)	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.	Up to ~ 32 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, based on local testing 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

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

Name	Role	Phone	Extension	Email
Toll Free Number	Contact	1-888-577-8839		Trialsites@msd.com

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Banner MD Anderson Cancer Center ( Site 0165)	Recruiting	Gilbert	Arizona	85234	United States

Label	URL
Merck Clinical Trials Information	View source

Ancestor Terms

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011246	Pregnadienetriols
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D054836	Indolizidines
D007212	Indolizines

ID	Term
D016393	Lymphoma, B-Cell
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D000069283	Rituximab
D003520	Cyclophosphamide
D004317	Doxorubicin
D011241	Prednisone
D011239	Prednisolone
D014750	Vincristine
D008775	Methylprednisolone