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)

March 20, 2024 updated by: Merck Sharp & Dohme LLC

A Multicenter, Open-label, Phase 2 Dose Escalation and Confirmation, and Efficacy Expansion Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP in Participants With DLBCL (waveLINE)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada, V8R 6V5
        • Recruiting
        • BC Cancer Victoria-Clinical Trials Unit ( Site 0105)
        • Contact:
          • Study Coordinator
          • Phone Number: 250-519-5500
    • Ontario
      • Toronto, Ontario, Canada, L6R3J7
        • Recruiting
        • William Osler Health System ( Site 0106)
        • Contact:
          • Study Coordinator
          • Phone Number: 9054942120
    • Quebec
      • Montreal, Quebec, Canada, H4J 1C5
        • Recruiting
        • Hopital du Sacre-Coeur de Montreal ( Site 0108)
        • Contact:
          • Study Coordinator
          • Phone Number: 514-338-2150
  • Israel
      • Jerusalem, Israel, 9112001
        • Recruiting
        • Hadassah Medical Center ( Site 0401)
        • Contact:
          • Study Coordinator
          • Phone Number: +97226779268
      • Ramat Gan, Israel, 5265601
        • Recruiting
        • Sheba Medical Center-Hemato Oncology ( Site 0400)
        • Contact:
          • Study Coordinator
          • Phone Number: 97235308401
  • Italy
      • Alessandria, Italy, 15121
        • Recruiting
        • Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant
        • Contact:
          • Study Coordinator
          • Phone Number: +390131206262
    • Lazio
      • Roma, Lazio, Italy, oo168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 0306)
        • Contact:
          • Study Coordinator
          • Phone Number: +390630154968
    • Lombardia
      • Milano, Lombardia, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele-Unità Linfomi ( Site 0305)
        • Contact:
          • Study Coordinator
          • Phone Number: +390226437649
    • Sicilia
      • Palermo, Sicilia, Italy, 90146
        • Recruiting
        • Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0307)
        • Contact:
          • Study Coordinator
          • Phone Number: +390916802773
    • Toscana
      • Firenze, Toscana, Italy, 50134
        • Recruiting
        • Azienda Ospedaliera Universitaria Careggi-SOD Ematologia ( Site 0308)
        • Contact:
          • Study Coordinator
          • Phone Number: +39055794 7958
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital ( Site 0201)
        • Contact:
          • Study Coordinator
          • Phone Number: +82220723559
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Samsung Medical Center ( Site 0200)
        • Contact:
          • Study Coordinator
          • Phone Number: +82234106548
  • Poland
    • Lodzkie
      • Łódź, Lodzkie, Poland, 93-513
        • Recruiting
        • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumat-Oddiał Hematologii Ogólnej ( Site 0503)
        • Contact:
          • Study Coordinator
          • Phone Number: +48426895191
    • Mazowieckie
      • Warszawa, Mazowieckie, Poland, 02-781
        • Recruiting
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site
        • Contact:
          • Study Coordinator
          • Phone Number: 22 546 22 23
    • Pomorskie
      • Gdańsk, Pomorskie, Poland, 80-214
        • Recruiting
        • Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0504)
        • Contact:
          • Study Coordinator
          • Phone Number: 58 584 43 57
    • Slaskie
      • Gliwice, Slaskie, Poland, 44-101
        • Recruiting
        • Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0505)
        • Contact:
          • Study Coordinator
          • Phone Number: +48322788523
  • Spain
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 0700)
        • Contact:
          • Study Coordinator
          • Phone Number: 915504800
    • Andalucia
      • Sevilla, Andalucia, Spain, 41013
        • Recruiting
        • HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Hematology ( Site 0704)
        • Contact:
          • Study Coordinator
          • Phone Number: 955012000
    • Barcelona
      • L'Hospitalet Del Llobregat, Barcelona, Spain, 08908
        • Recruiting
        • Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 0703)
        • Contact:
          • Study Coordinator
          • Phone Number: 34932607750
  • Turkey
      • Ankara, Turkey, 06620
        • Recruiting
        • Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 0801)
        • Contact:
          • Study Coordinator
          • Phone Number: +90 5055025050
      • Edirne, Turkey, 22030
        • Recruiting
        • Trakya University ( Site 0805)
        • Contact:
          • Study Coordinator
          • Phone Number: 905335544797
    • Istanbul
      • Stanbul, Istanbul, Turkey, 34214
        • Active, not recruiting
        • Mega Medipol-Hematology ( Site 0808)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 positron emission tomography (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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation
Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m^2 cyclophosphamide, 50 mg/m^2 doxorubicin, and 375 mg/m^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months).
Biological: Rituximab
IV infusion
Other Names:
  • RITUXAN®
Biological: Zilovertamab Vedotin
IV infusion
Other Names:
  • MK-2140
  • VLS-101
Drug: Cyclophosphamide
IV infusion
Other Names:
  • CYTOXAN®
  • NEOSAR®
Drug: Doxorubicin
IV infusion
Other Names:
  • ADRIAMYCIN®
Biological: Rituximab Biosimilar
IV infusion
Other Names:
  • TRUXIMA®
Drug: Prednisone
IV or oral administration (per local guidelines)
Drug: Prednisolone
IV or oral administration (per local guidelines)
Experimental: Zilovertamab Vedotin + R-CHP: Efficacy Expansion
Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m^2 cyclophosphamide, 50 mg/m^2 doxorubicin, and 375 mg/m^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months).
Biological: Rituximab
IV infusion
Other Names:
  • RITUXAN®
Biological: Zilovertamab Vedotin
IV infusion
Other Names:
  • MK-2140
  • VLS-101
Drug: Cyclophosphamide
IV infusion
Other Names:
  • CYTOXAN®
  • NEOSAR®
Drug: Doxorubicin
IV infusion
Other Names:
  • ADRIAMYCIN®
Biological: Rituximab Biosimilar
IV infusion
Other Names:
  • TRUXIMA®
Drug: Prednisone
IV or oral administration (per local guidelines)
Drug: Prednisolone
IV or oral administration (per local guidelines)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) in Cycle 1
Time Frame: Cycle 1 (up to 21 days)
DLTs will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and are defined as any drug-related adverse event (AE) observed during the DLT evaluation period (e.g. Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle. The number of participants with DLTs in Cycle 1 will be reported.
Cycle 1 (up to 21 days)
Number of Participants Who Experienced At Least One Adverse Event (AE)
Time Frame: Up to approximately 42 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.
Up to approximately 42 months
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Time Frame: Up to approximately 5.5 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
Up to approximately 5.5 months
Complete Response Rate (CRR) per Lugano Response Criteria
Time Frame: Up to approximately 42 months
CRR is defined as the percentage of participants who achieve a Complete Response (CR) per Lugano response criteria [Cheson, B. D., et al 2014] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with computed tomography (CT) or magnetic resonance imaging (MRI), metabolic imaging with positron emission tomography (PET), and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with CRR will be reported.
Up to approximately 42 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) per Lugano Response Criteria
Time Frame: Up to approximately 42 months
ORR is defined as the percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) per Lugano response criteria [Cheson, B. D., et al 2014] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with computed tomography (CT) or magnetic resonance imaging (MRI), metabolic imaging with positron emission tomography (PET), and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with ORR will be reported.
Up to approximately 42 months
Duration of Response (DOR) per Lugano Response Criteria
Time Frame: Up to approximately 42 months
For participants who demonstrate a confirmed Complete Response (CR) or Partial Response (PR) per Lugano response criteria [Cheson, B. D., et al 2014] for malignant lymphoma, DOR is 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. CR and PR assessment includes anatomic imaging with computed tomography (CT) or magnetic resonance imaging (MRI), metabolic imaging with positron emission tomography (PET), and clinical findings including physical examination and bone marrow biopsy results. DOR as assessed by the investigator will be reported.
Up to approximately 42 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 14, 2022

Primary Completion (Estimated)

January 26, 2026

Study Completion (Estimated)

January 26, 2026

Study Registration Dates

First Submitted

June 1, 2022

First Submitted That Met QC Criteria

June 1, 2022

First Posted (Actual)

June 6, 2022

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 20, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2140-007
  • MK-2140-007 (Other Identifier: Merck)
  • 2021-005861-41 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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