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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)

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ClinicalTrials.gov Identifier: NCT05406401
Recruitment Status : Recruiting
First Posted : June 6, 2022
Last Update Posted : January 20, 2023
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Lymphoma, Large B-Cell, Diffuse (DLBCL) Biological: Zilovertamab Vedotin Drug: Cyclophosphamide Drug: Doxorubicin Biological: Rituximab Biological: Rituximab Biosimilar Drug: Prednisone Drug: Prednisolone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : July 14, 2022
Estimated Primary Completion Date : January 26, 2026
Estimated Study Completion Date : January 26, 2026


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: Zilovertamab Vedotin
IV infusion
Other Names:
  • MK-2140
  • VLS-101

Drug: Cyclophosphamide
IV infusion
Other Names:
  • CYTOXAN®
  • NEOSAR®

Drug: Doxorubicin
IV infusion
Other Name: ADRIAMYCIN®

Biological: Rituximab
IV infusion
Other Name: RITUXAN®

Biological: Rituximab Biosimilar
IV infusion
Other Name: 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: Zilovertamab Vedotin
IV infusion
Other Names:
  • MK-2140
  • VLS-101

Drug: Cyclophosphamide
IV infusion
Other Names:
  • CYTOXAN®
  • NEOSAR®

Drug: Doxorubicin
IV infusion
Other Name: ADRIAMYCIN®

Biological: Rituximab
IV infusion
Other Name: RITUXAN®

Biological: Rituximab Biosimilar
IV infusion
Other Name: TRUXIMA®

Drug: Prednisone
IV or oral administration (per local guidelines)

Drug: Prednisolone
IV or oral administration (per local guidelines)




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



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

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

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): NCT05406401


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

Locations
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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: NCT05406401    
Other Study ID Numbers: 2140-007
MK-2140-007 ( Other Identifier: Merck )
2021-005861-41 ( EudraCT Number )
First Posted: June 6, 2022    Key Record Dates
Last Update Posted: January 20, 2023
Last Verified: January 2023
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
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Prednisone
Prednisolone
Cyclophosphamide
Rituximab
Doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents