Merck,MK2140-010,Ph 3,Randomized, Lymphoma, Zilovertamab vedotin + R-CHP vs R-Chop

What is the Purpose of this Study?

Primary Objective: To compare zilovertamab vedotin plus R-CHP with R-CHOP with respect to progression-free survival (PFS) per Lugano response criteria as assessed by blinded independent central review (BICR). Hypothesis (H1): Zilovertamab vedotin plus R-CHP is superior to R-CHOP with respect to PFS per Lugano response criteria as assessed by BICR. To compare zilovertamab vedotin plus R-CHP with R-CHOP with respect to complete response (CR) rate at end of treatment (EoT) per Lugano response criteria as assessed by BICR. Hypothesis (H2): Zilovertamab vedotin plus R-CHP is superior to R-CHOP with respect to confirmed CR rate at EoT per Lugano response criteria as assessed by BICR. Secondary Objectives: To compare zilovertamab vedotin plus R-CHP with R-CHOP with respect to overall survival (OS). Hypothesis (H3): Zilovertamab vedotin plus R-CHP is superior to R-CHOP with respect to OS. To evaluate event-free survival (EFS) with zilovertamab vedotin plus R-CHP versus R-CHOP per Lugano response criteria as assessed by BICR. To evaluate the duration of CR of zilovertamab vedotin plus R-CHP versus R-CHOP. To evaluate the safety and tolerability of zilovertamab vedotin plus R-CHP. To evaluate changes from baseline in health-related QoL assessments using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and FACT/GOG-NTX. To evaluate time to deterioration (TTD) in health-related QoL assessments using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and FACT/GOG-NTX.

Eligibility

* 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

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

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Where can I participate?

CS Cancer at Beverly Hills
CS Cancer at Cedars-Sinai Medical Center

More about this Clinical Trial

What is the full name of this clinical trial?

MK2140-010: A Randomized, Open-Label, Multicenter, Phase 3 Study of Zilovertamab Vedotin in Combination With R-CHP Versus R-CHOP in Participants With Previously Untreated Diffuse Large B-Cell Lymphoma

Study Details

Disease Type/Condition

Other Hematopoietic

Principal Investigator

Darrah, Justin

Co-Investigators

Akil Merchant, Barry Rosenbloom, David Hoffman, Jeremy Lorber, Joshua Sasine, Kevin Scher, Sepehr Rokhsar

Age Group

Adult

Phase

III

IRB Number

STUDY00003859

ClinicalTrials.gov ID

NCT06717347

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org