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 |
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Recruitment Status :
Recruiting
First Posted : June 6, 2022
Last Update Posted : January 20, 2023
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Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
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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 |
| 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 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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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).
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Biological: Zilovertamab Vedotin
IV infusion
Other Names:
Drug: Cyclophosphamide IV infusion
Other Names:
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) |
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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).
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Biological: Zilovertamab Vedotin
IV infusion
Other Names:
Drug: Cyclophosphamide IV infusion
Other Names:
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 :
- 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.
- 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.
- 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.
- 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 :
- 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.
- 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
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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
| Contact: Toll Free Number | 1-888-577-8839 | Trialsites@merck.com |
Locations
Show 20 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Additional Information:
| 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 |
| 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 |