A Phase 2/3 interventional study of Zilovertamab vedotin and Rituximab in DLBCL and Diffuse Large B-Cell Lymphoma, sponsored by Merck Sharp & Dohme LLC. Recruiting at 135 sites in 26 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-03.
Sponsored by Merck Sharp & Dohme LLC (part of Merck & Co., Inc) · Phase 2/3, Interventional, and Treatment
The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in combination with standard of care options for the treatment of rrDLBCL. This study will be divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx with respect to progression-free survival (PFS) per Lugano response criteria by blinded independent review committee (BICR); and that ZV in combination with bendamustine rituximab (BR) is superior to BR with respect to PFS per Lugano response criteria by BICR.
With protocol amendment 4 (effective: 04-April-2024), enrollment in Cohort B (study arms Bendamustine Rituximab [BR] and ZV + BR) is discontinued. No efficacy outcome analysis and hypothesis testing will be conducted for Cohort B.
1,868 studies on the registry are indexed under Lymphoma, Large B-Cell, Diffuse; 355 are open to participants now.
This study's planned enrollment of 290 is above the median of 45 across 1,497 interventional studies indexed under Lymphoma, Large B-Cell, Diffuse.
Browse Lymphoma, Large B-Cell, Diffuse studies →Merck Sharp & Dohme LLC is the lead sponsor of 2,166 studies on the registry; 132 are open to participants now.
Of its 501 completed or terminated interventional studies of FDA-regulated products, 370 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Zilovertamab vedotin plus R-GemOx, or R-GemOx study arms:
Not applicable with protocol amendment 4: Zilovertamab vedotin plus Bendamustine Rituximab (BR), and Bendamustine Rituximab study arms:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Gemcitabine 1000 mg/m\^2 and Oxaliplatin 100 mg/m\^2 (R-GemOx) given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles.
Biological: Zilovertamab vedotin · Biological: Rituximab · Drug: Gemcitabine · Drug: Oxaliplatin · Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
Using the recommended Phase 2 dose (RP2D) dose of ZV plus R-GemOx from Part 1, participants will receive ZV plus R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
Biological: Zilovertamab vedotin · Biological: Rituximab · Drug: Gemcitabine · Drug: Oxaliplatin · Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
Participants will receive R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
Biological: Rituximab · Drug: Gemcitabine · Drug: Oxaliplatin
Using RP2D from Part 1, participants will receive ZV plus Rituximab 375 mg/m\^2, given intravenously on Day 1 and Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2, of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
Biological: Zilovertamab vedotin · Biological: Rituximab · Drug: Bendamustine · Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
Participants will receive Rituximab 375 mg/m\^2, given intravenously on Day 1 Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.
Biological: Rituximab · Drug: Bendamustine
Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Bendamustine 90 mg/m\^2 (BR) given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles.
Biological: Zilovertamab vedotin · Biological: Rituximab · Drug: Bendamustine · Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
Also known as: MK-2140, VLS-101
IV Infusion 375 mg/m\^2
Also known as: Rituxan®/mabthera, Truxima® (rituximab-abbs), RUXIENCE®, RIABNI®
IV Infusion 1000 mg/m\^2
Also known as: Gemzar®
IV Infusion 100 mg/m\^2
Also known as: Eloxatin®
IV Infusion 90 mg/m\^2
Also known as: Bendeka®, Treanda®, Belrapzo®
Prophylactic G-CSF will be administered at each cycle of zilovertamab vedotin as per the institutional guidelines.
Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1
The CTCAE, Version 5.0 will be used to grade the severity of AEs in this study. DLTs will be reported for Part 1 of this study.
Time frame: Up to ~6 weeks
Number of participants who experienced an adverse event (AE)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE will be reported.
Time frame: Up to ~68 months
Number of participants who discontinued study treatment due to an AE
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued study treatment due to an AE will be reported.
Time frame: Up to ~68 months
Overall survival (OS)
OS, defined as the time from randomization to death due to any cause will be reported.
Time frame: Up to ~35 months
Progression-free survival (PFS)
PFS, defined as the time from randomization to the first documented disease progression per Lugano response criteria as assessed by BICR or death due to any cause, whichever occurs first will be presented.
Time frame: Up to ~35 months
Objective response rate (ORR)
ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano criteria as assessed by BICR will be presented.
Time frame: Up to ~35 months
Duration of response (DOR)
DOR, defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first, will be reported.
Time frame: Up to ~35 months
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Showing the first 100 of 135 sites across 26 countries. Choose a country and city above to see the rest.
Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Data sharing details ↗ · externaldatasharing-msd.com
Started Jan 2022 (actual). Primary completion is estimated for Sep 2027, 68 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
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Studies of the drugs tested here: Zilovertamab vedotin · Gemcitabine · Oxaliplatin · Bendamustine
Lymphoma, Large B-Cell, Diffuse →