A clinical study of zilovertamab vedotin with R-CHP treatment in people with diffuse large B-cell lymphoma (MK-2140-011)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 May 2025 → ongoing

Decision date (initial)

2025-05-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-515526-89-00

WHO UTN

U1111-1309-2852

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Therapy, Pharmacokinetic

1. To compare zilovertamab vedotin plus R-CHP with polatuzumab vedotin plus R-CHP with respect to CR rate at EOT per Lugano response criteria as assessed by BICR.

Secondary objectives 5

1. To compare zilovertamab vedotin plus R-CHP with polatuzumab vedotin plus R-CHP with respect to PFS per Lugano response criteria as assessed by BICR.
2. To compare zilovertamab vedotin plus R-CHP with polatuzumab vedotin plus R-CHP with respect to OS.
3. To evaluate EFS with zilovertamab vedotin plus R-CHP versus polatuzumab vedotin plus R-CHP per Lugano response criteria as assessed by BICR.
4. To evaluate the DurCR of zilovertamab vedotin plus R-CHP versus polatuzumab vedotin plus R-CHP per Lugano response criteria as assessed by BICR.
5. To evaluate the safety and tolerability of zilovertamab vedotin plus R-CHP. To evaluate change from baseline in HRQoL and symptoms for zilovertamab vedotin plus R-CHP versus polatuzumab vedotin plus R-CHP using the FACT-Lym and FACT/GOG-NTX.

Conditions and MedDRA coding

Diffuse Large B-Cell Lymphoma (DLBCL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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
2. Has positron emission tomography (PET) positive disease at screening, defined as 4 to 5 on the Lugano 5-point scale
3. Has received no prior treatment for their DLBCL
4. Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART)
5. 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
6. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

Exclusion criteria 15

1. Has a history of transformation of indolent disease to DLBCL
2. Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL) or Grey zone lymphoma
3. Has Ann Arbor Stage I DLBCL
4. 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
5. Has clinically significant pericardial or pleural effusion
6. Has ongoing Grade >1 peripheral neuropathy
7. Has a demyelinating form of Charcot-Marie-Tooth disease
8. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
9. Has ongoing corticosteroid therapy
10. Known additional malignancy that is progressing or has required active treatment within the past 2 years
11. Known active central nervous system (CNS) lymphoma
12. Has active autoimmune disease that has required systemic treatment in the past 2 years
13. Has active infection requiring systemic therapy
14. 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
15. Has history of stem cell/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete Response Rate (CRR) at End of Treatment (EOT) per Lugano Response Criteria

Secondary endpoints 10

1. Progression-free Survival (PFS) per Lugano Response Criteria
2. Overall Survival (OS)
3. Event-free Survival (EFS) per Lugano Response Criteria
4. Duration of CR
5. Number of Participants Who Experienced At Least One Adverse Event (AE)
6. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
7. Change From Baseline in Health-Related Quality Of Life (HRQoL) on Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Trial Outcome Index (TOI)
8. Change From Baseline in HRQoL on FACT-Lym Total Score
9. Change From Baseline in HRQoL on FACT-Lym Physical Well-being (PWB), Items General Physical (GP)1 through GP7
10. Change From Baseline in HRQoL on Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) Neurotoxicity Subscale Score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Puja Patel

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Puja Patel

Third parties 8

Locations

5 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications