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Trial record 1 of 1 for:    A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK- 2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
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A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

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ClinicalTrials.gov Identifier: NCT05139017
Recruitment Status : Recruiting
First Posted : December 1, 2021
Last Update Posted : May 22, 2024
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
DLBCL Diffuse Large B-Cell Lymphoma Biological: Zilovertamab vedotin Biological: Rituximab Drug: Gemcitabine Drug: Oxaliplatin Drug: Bendamustine Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: In Part 1, Dose Confirmation will be determined by modified toxicity probability interval (mTPI) design, where participants will be assigned to two treatment groups, cohort: A (zilovertamab vedotin in combinatio with R-GemOx) in parallel with cohort B (zilovertamab vedotin in combination with BR). Part 2 will be an Efficacy Expansion (cohorts A & B) where all participants in each cohort will be assigned to 2 treatment groups for the duration of the study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-003)
Actual Study Start Date : January 14, 2022
Estimated Primary Completion Date : June 21, 2027
Estimated Study Completion Date : June 21, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: ZV + R-GemOx (Part 1)
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
Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
Other Names:
  • MK-2140
  • VLS-101

Biological: Rituximab
IV Infusion 375 mg/m^2
Other Names:
  • Rituxan®/mabthera
  • Truxima® (rituximab-abbs)
  • RUXIENCE®)

Drug: Gemcitabine
IV Infusion 1000 mg/m^2
Other Name: Gemzar®

Drug: Oxaliplatin
IV Infusion 100 mg/m^2
Other Name: Eloxatin®

Experimental: ZV + R-GemOx (Part 2)
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
Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
Other Names:
  • MK-2140
  • VLS-101

Biological: Rituximab
IV Infusion 375 mg/m^2
Other Names:
  • Rituxan®/mabthera
  • Truxima® (rituximab-abbs)
  • RUXIENCE®)

Drug: Gemcitabine
IV Infusion 1000 mg/m^2
Other Name: Gemzar®

Drug: Oxaliplatin
IV Infusion 100 mg/m^2
Other Name: Eloxatin®

Active Comparator: R-GemOx (active control for Part 2)
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
IV Infusion 375 mg/m^2
Other Names:
  • Rituxan®/mabthera
  • Truxima® (rituximab-abbs)
  • RUXIENCE®)

Drug: Gemcitabine
IV Infusion 1000 mg/m^2
Other Name: Gemzar®

Drug: Oxaliplatin
IV Infusion 100 mg/m^2
Other Name: Eloxatin®

Experimental: ZV + BR (Part 2)
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
Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
Other Names:
  • MK-2140
  • VLS-101

Biological: Rituximab
IV Infusion 375 mg/m^2
Other Names:
  • Rituxan®/mabthera
  • Truxima® (rituximab-abbs)
  • RUXIENCE®)

Drug: Bendamustine
IV Infusion 90 mg/m^2
Other Names:
  • Bendeka®
  • Treanda®
  • Belrapzo®

Active Comparator: Bendamustine Rituximab (BR)
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
IV Infusion 375 mg/m^2
Other Names:
  • Rituxan®/mabthera
  • Truxima® (rituximab-abbs)
  • RUXIENCE®)

Drug: Bendamustine
IV Infusion 90 mg/m^2
Other Names:
  • Bendeka®
  • Treanda®
  • Belrapzo®

Experimental: ZV + BR (Part 1)
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
Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
Other Names:
  • MK-2140
  • VLS-101

Biological: Rituximab
IV Infusion 375 mg/m^2
Other Names:
  • Rituxan®/mabthera
  • Truxima® (rituximab-abbs)
  • RUXIENCE®)

Drug: Bendamustine
IV Infusion 90 mg/m^2
Other Names:
  • Bendeka®
  • Treanda®
  • Belrapzo®




Primary Outcome Measures :
  1. Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1 [ Time Frame: Up to ~6 weeks ]
    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.

  2. Number of participants who experienced an adverse event (AE) [ Time Frame: Up to ~34 months ]
    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.

  3. Number of participants who discontinued study treatment due to an AE [ Time Frame: Up to ~34 months ]
    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.

  4. PFS [ Time Frame: Up to ~27 months ]
    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.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to ~34 months ]
    OS, defined as the time from randomization to death due to any cause will be reported.

  2. Objective response rate (ORR) [ Time Frame: Up to ~19 months ]
    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.

  3. Duration of response (DOR) [ Time Frame: Up to ~27 months ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL).
  • Has radiographically measurable DLBCL per the Lugano response criteria, as assessed locally by the investigator.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to study treatment initiation.
  • Has adequate organ function.
  • Is able to provide new or archival tumor tissue sample not previously irradiated.

Zilovertamab vedotin plus R-GemOx, or R-GemOx study arms:

  • Has relapsed or refractory DLBCL and is ineligible for or have failed autologous stem-cell transplant (ASCT) and have failed at least 1 line of prior therapy.
  • Has post-chimeric antigen receptor T (post-CAR-T) cell therapy failure or is ineligible for CAR-T cell therapy.

Not applicable with protocol amendment 4: Zilovertamab vedotin plus Bendamustine Rituximab (BR), and Bendamustine Rituximab study arms:

  • Has relapsed or refractory DLBCL and is ineligible for or have failed ASCT and have failed at least 2 lines of prior therapy.
  • Has post-CAR-T therapy failure or is ineligible for CAR-T cell therapy.

Exclusion Criteria:

  • Not applicable with protocol amendment 4: Has 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 or serious cardiac arrhythmia requiring medication.
  • Has ongoing graft-versus-host disease (GVHD) of any grade, or is receiving treatment for their GVHD.
  • Has pericardial effusion or clinically significant pleural effusion.
  • Has ongoing Grade >1 peripheral neuropathy.
  • Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
  • Has a demyelinating form of Charcot-Marie-Tooth disease.
  • Has contraindication to any of the study intervention components due to prior anaphylactic reaction.
  • Has received prior systemic anticancer therapy, including investigational agents within 4 weeks prior to the first dose of study intervention.
  • Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • Has ongoing corticosteroid therapy.
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
  • Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission.
  • 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 psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05139017


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 42 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
Additional Information:
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT05139017    
Other Study ID Numbers: 2140-003
VLS-101 ( Other Identifier: Velos Bio )
MK-2140-003 ( Other Identifier: Merck )
waveLINE-003 ( Other Identifier: Merck )
2022-502646-27-00 ( Registry Identifier: EU CT )
First Posted: December 1, 2021    Key Record Dates
Last Update Posted: May 22, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Gemcitabine
Oxaliplatin
Bendamustine Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents