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)

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.


Eligibility Criteria:
The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion:

* Has histologically confirmed diagnosis of DLBCL by prior biopsy
* Has PET-positive disease verified by blinded independent central review (BICR) at screening, defined as 4-5 on the Lugano response criteria 5-point scale
* Has received no prior treatment for DLBCL
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days prior to the start of study intervention

Exclusion:

* Has a history of transformation of indolent disease to DLBCL
* Has received solid organ transplant at any time
* Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL)
* Has clinically significant (ie, 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 pericardial effusion or clinically significant pleural effusion
* Has ongoing Grade \>1 peripheral neuropathy
* Has a demyelinating form of Charcot-Marie-Tooth disease
* History of a second malignancy unless potentially curative treatment has been completed with no evidence of malignancy for 2 years with the exception of participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous-cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder
* Has received prior radiotherapy within 28 days of start of study intervention
* Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent)
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has received a strong inhibitor or inducer of CYP3A4 (including itraconazole, ketoconazole, posaconazole, or voriconazole) within 7 days prior to the start of study intervention or expected requirement for chronic use of a strong CYP3A4 inhibitor until \<30 days after the last dose
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days before the first dose of study intervention
* Has known active central nervous system (CNS) lymphoma
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known active hepatitis C virus infection
* Has a known active hepatitis B virus infection