A clinical study of zilovertamab vedotin in people with large B-cell lymphoma (MK-2140-010)

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

19 Mar 2025 → ongoing

Decision date (initial)

2025-02-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-515566-13-00

WHO UTN

U1111-1309-3971

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Efficacy, Therapy

To compare zilovertamab vedotin plus R-CHP with R-CHOP with respect to PFS per Lugano response criteria as assessed by BICR.

Secondary objectives 6

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

Conditions and MedDRA coding

Diffuse Large B-Cell Lymphoma (DLBCL)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, according to the 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. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before randomization.
5. Has an ejection fraction ≥45% as determined by either echocardiogram (ECHO) or multigated acquisition (MUGA)
6. Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART)
7. 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
8. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

Exclusion criteria 16

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. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
11. Known additional malignancy that is progressing or has required active treatment within the past 2 years
12. Known active central nervous system (CNS) lymphoma.
13. Has active autoimmune disease that has required systemic treatment in the past 2 years
14. Has active infection requiring systemic therapy.
15. 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.
16. Has history of allogeneic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free Survival (PFS) per Lugano Response Criteria

Secondary endpoints 10

1. Complete Response (CR) at End of Treatment (EOT) 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) Score
8. Change From Baseline in HRQoL on FACT-Lym Total Score
9. Change From Baseline in HRQoL on FACT-Lym Physical Wellbeing (PWB) score
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 6

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

Nishitha Reddy

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Nishitha Reddy

Third parties 7

Locations

11 EU/EEA countries · 72 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 104 files

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

Application history

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