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)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05139017
Collaborator
(none)
420
16
5
35.1
26.3
0.7

Study Details

Study Description

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 Safety Run-in 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.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
420 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
In Part 1, Dose Confirmation, determined by modified toxicity probability interval (mTPI) design, all participants will be assigned to one treatment group. In Part 2: There will be 2 cohorts: A and B, consisting of Safety Run-in (cohort B) and Efficacy Expansion (cohorts A & B). In the Safety Run-in all participants will be assigned to one treatment group and in Efficacy Expansion, all participants in each cohort will be assigned to 2 treatment groups for the duration of study.In Part 1, Dose Confirmation, determined by modified toxicity probability interval (mTPI) design, all participants will be assigned to one treatment group. In Part 2: There will be 2 cohorts: A and B, consisting of Safety Run-in (cohort B) and Efficacy Expansion (cohorts A & B). In the Safety Run-in all participants will be assigned to one treatment group and in Efficacy Expansion, all participants in each cohort will be assigned to 2 treatment groups for the duration of 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
Actual Study Start Date :
Jan 14, 2022
Anticipated Primary Completion Date :
Dec 16, 2024
Anticipated Study Completion Date :
Dec 16, 2024

Arms and Interventions

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)
  • Drug: Gemcitabine
    IV Infusion 1000 mg/m^2
    Other Names:
  • Gemzar®
  • Drug: Oxaliplatin
    IV Infusion 100 mg/m^2
    Other Names:
  • 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)
  • Drug: Gemcitabine
    IV Infusion 1000 mg/m^2
    Other Names:
  • Gemzar®
  • Drug: Oxaliplatin
    IV Infusion 100 mg/m^2
    Other Names:
  • 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)
  • Drug: Gemcitabine
    IV Infusion 1000 mg/m^2
    Other Names:
  • Gemzar®
  • Drug: Oxaliplatin
    IV Infusion 100 mg/m^2
    Other Names:
  • 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)
  • 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)
  • Drug: Bendamustine
    IV Infusion 90 mg/m^2
    Other Names:
  • Bendeka®
  • Treanda®
  • Belrapzo®
  • Outcome Measures

    Primary Outcome Measures

    1. Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1 [Up to ~2 cycles (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) [Up to ~6 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 [Up to ~6 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 [Up to ~36 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) [Up to ~36 months]

      OS, defined as the time from randomization to death due to any cause will be reported.

    2. Objective response rate (ORR) [Up to ~36 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) [Up to ~36 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Has a histologically confirmed diagnosis of 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.

    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:
    • 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.

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Innovative Clinical Research Institute ( Site 0122) Whittier California United States 90603
    2 Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133) Louisville Kentucky United States 40207
    3 Louisiana State University Health Sciences Center New Orleans ( Site 0134) New Orleans Louisiana United States 70112
    4 University of Maryland ( Site 0123) Baltimore Maryland United States 21201
    5 University of Massachusetts Medical School ( Site 0119) Worcester Massachusetts United States 01655
    6 St. Vincent Frontier Cancer Center-Research ( Site 0108) Billings Montana United States 59102
    7 New York Medical College ( Site 0113) Valhalla New York United States 10595
    8 Pitie Salpetriere University Hospital-Clinical haematology ( Site 0700) Paris France 75013
    9 Hadassah Medical Center ( Site 1100) Jerusalem Israel 9112001
    10 Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1203) Rozzano Milano Italy 20089
    11 Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1202) Napoli Italy 80131
    12 Pratia MCM Krakow ( Site 1303) Krakow Malopolskie Poland 30-510
    13 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( S Warszawa Mazowieckie Poland 02-781
    14 Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1302) Gdynia Pomorskie Poland 81-519
    15 Ankara University Hospital Cebeci-hematology ( Site 1901) Ankara Turkey 06100
    16 Ondokuz Mayıs Universitesi ( Site 1907) Samsun Turkey 55139

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT05139017
    Other Study ID Numbers:
    • 2140-003
    • VLS-101
    First Posted:
    Dec 1, 2021
    Last Update Posted:
    Aug 15, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 15, 2022