Clinical trial NCT06890884: A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBCL) (MK-2140-011/waveLINE-011)
Official title: A Randomized, Open-label, Multicenter, Phase 2 Study Evaluating the Efficacy and Safety of Zilovertamab Vedotin (MK-2140) Plus R-CHP Versus Polatuzumab Vedotin Plus R-CHP in Treatment-naïve Participants With GCB Subtype of Diffuse Large B-cell Lymphoma (DLBCL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lymphoma, Large B-Cell, Diffuse
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2025-03-24
Enrollment: 594
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Researchers are looking for ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL). DLBCL is a fast-growing blood cancer that affects B-cells. GCB is a type of DLBCL that affects young B-cells that are still maturing.

The goal of this study is to learn if more people who receive zilovertamab vedotin (MK-2140) and R-CHP have the cancer respond (go away) than those who receive polatuzumab vedotin and R-CHP.


Eligibility criteria: Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has histologically confirmed diagnosis of germinal center B-cell (GCB) subtype of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, according to the World Health Organization (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.
* Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART).
* Participants 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:

The main exclusion criteria include but are not limited to the following:

* 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.
* 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 active HBV (defined as HBsAg positive and detectable HBV deoxyribonucleic acid (DNA)) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid (RNA)) infection.
* Has history of stem cell/solid organ transplant.

Primary outcomes:
measure: Complete Response Rate (CRR) at End of Treatment (EOT) per Lugano Response Criteria
timeFrame: Up to approximately 31 months
Secondary outcomes:
measure: Progression-free Survival (PFS) per Lugano Response Criteria
timeFrame: Up to approximately 51 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 87 months
measure: Event-free Survival (EFS) per Lugano Response Criteria
timeFrame: Up to approximately 51 months
measure: Duration of CR
timeFrame: Up to approximately 51 months
measure: Number of participants who experience one or more adverse events (AEs)
timeFrame: Up to approximately 9 months
measure: Number of participants who discontinue study intervention due to an AE
timeFrame: Up to approximately 6 months
measure: Change From Baseline in Health-Related Quality Of Life (HRQoL) on Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Trial Outcome Index (TOI)
timeFrame: Baseline and up to Week 25
measure: Change From Baseline in HRQoL on FACT-Lym Total Score
timeFrame: Baseline and up to Week 25
measure: Change From Baseline in HRQoL on FACT-Lym Physical Well-being (PWB) (Items General Physical [GP]1 through GP7)
timeFrame: Baseline and up to Week 25
measure: Change From Baseline in HRQoL on Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) Neurotoxicity Subscale Score
timeFrame: Baseline and up to Week 25
Other outcomes:
Locations:
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont ( Site 0304)
state: Hainaut
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 0604)
city: Jerusalem
country: Israel
facility: Haddasah Medical Center ( Site 0601)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 0603)
city: Meldola
country: Italy
facility: IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 0707)
state: Forli-Cesena
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia ( Site 0701)
city: Napoli
country: Italy
facility: Universita degli Studi di Napoli Federico II ( Site 0705)
city: Palermo
country: Italy
facility: Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO ( Site 0702)
city: Karkow
country: Poland
facility: Pratia MCM Krakow ( Site 0804)
state: Malopolskie
city: Nowy Sącz
country: Poland
facility: Szpital Specjalistyczny im. Jedrzeja Sniadeckiego w Nowym Saczu ( Site 0806)
state: Malopolskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0803)
state: Mazowieckie
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: