Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

Rare Diseases

Leukemia

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Aggression

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

Richter Syndrome

Participants will receive zilovertamab vedotin 2.5 mg/kg every 3 weeks (Q3W) until disease progression or discontinuation.

Participants will receive zilovertamab vedotin every 3 weeks (Q3W) combined with nemtabrutinib daily until disease progression or discontinuation.

Participants will receive either zilovertamab vedotin 2.5 mg/kg every 3 weeks (Q3W) or 2.0 mg/kg with infusions on Days 1 and 8 of each 3 week cycle (Q2/3W) until disease progression or discontinuation.

Zilovertamab vedotin

Nemtabrutinib

Toll Free Number

Study Coordinator

Medical Director

The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination in participants with select B-cell lymphomas including mantle cell lymphoma (MCL), Richter's transformation lymphoma (RTL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). This study will also evaluate zilovertamab vedotin as monotherapy and in combination with respect to objective response rate.

* Cohort A: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor (BTKi), and post therapy chimeric antigen receptor T (CAR-T) cell therapy or ineligible for CAR-T cell therapy
* Cohort B: Participants with relapsed or refractory RT disease after at least 1 prior systemic therapy
* Cohort C: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi
* Cohort D: Participants with relapsed or refractory FL and CLL relapsed or refractory disease after at least 2 prior systemic therapies and have no other available therapy
* Cohort E: Participants with relapsed or refractory FL after at least 2 prior systemic therapies and have no other available therapy
* Cohort F: Participants with relapsed or refractory CLL after at least 2 prior systemic therapies and have no other available therapy

The primary study hypothesis is that zilovertamab vedotin monotherapy has an increased Objective Response Rate (ORR) per Lugano Response Criteria as assessed by blinded independent central review (BICR).

A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)

A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies

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

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 percentage of participants with MCL, FL, and CLL who experienced an AE will be reported.

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 percentage of participants with MCL, FL, and CLL who discontinued study treatment due to an AE will be reported.

The Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 will be used to grade the severity of AEs. DLTs for participants with MCL as assessed by investigator will be reported.

ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano Response Criteria as assessed by BICR will be reported.

ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano Response Criteria as assessed by investigator will be reported.

ORR, defined as the percentage of participants who achieve a CR or PR per iwCLL criteria as assessed by investigator will be reported.

DOR, defined as the time from the first documented evidence of CR or PR per Lugano Response Criteria as assessed by BICR, until disease progression or death due to any cause, whichever occurs first, will be reported.

DOR, defined as the time from the first documented evidence of CR or PR per Lugano Response Criteria as assessed by investigator, until disease progression or death due to any cause, whichever occurs first, will be reported.

DOR, defined as the time from the first documented evidence of CR or PR per iwCLL criteria as assessed by investigator, until disease progression or death due to any cause, whichever occurs first, will be reported.

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 percentage of participants with MCL, RTL, FL, and CLL who experienced an AE will be reported.

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 percentage of participants with MCL, RTL, FL, and CLL who discontinued study treatment due to an AE will be reported.

Merck Sharp & Dohme LLC

Infections

Heart and Blood Diseases

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Lymphoma, T-Cell

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Burkitt Lymphoma

Waldenstrom Macroglobulinemia

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Acute Graft Versus Host Disease

Participants will be administered escalating doses of zilovertamab vedotin at 0.50, 1.00, 1.50, 2.25, 2.50, 2.75, and 3.00 mg/kg IV on Day 1 of repeated 21-day cycles (Q1/3W).

Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1 and 8 of repeated 21-day cycles (Q2/3W).

Participants will be administered escalating doses of zilovertamab vedotin at 0.75, 1.00, 1.25, 1.50, 1.75, 2.00, and 2.25 mg/kg IV on Day 1, 8, and 15 of repeated 21-day cycles (Q3/4W).

Zilovertamab vedotin administered via IV infusion per Schedule 1, 2, or 3 according to participant allocation.

The purpose of this study is to evaluate the safety, pharmacokinetics, immunogenicity, and efficacy of zilovertamab vedotin given intravenously (IV) across a range of dose levels in participants with previously treated hematological cancers including acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Burkitt lymphoma (BL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), Richter transformation lymphoma (RTL), and T-cell non-Hodgkin lymphoma (NHL).

Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher dose levels within each dose schedule of zilovertamab vedotin using a 3+3 dose-escalation design.

A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)

A Phase 1 Dose-Escalation and Cohort-Expansion Study of VLS-101 in Subjects With Hematological Malignancies (waveLINE-001)

Participants will receive zilovertamab vedotin according to Schedule 1, 2, or 3. The MTD will be determined by the number of participants who experience a dose limiting toxicity (DLT). The MTD will be defined as the highest tested dose level at which ≥6 participants have been treated and which is associated with a Cycle 1 DLT in ≤17% of the participants.

Selection of the RDR will be based on consideration of short- and long-term safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The RDR may be the MTD or may be a lower dose within the tolerable dose range.

Zilovertamab vedotin drug administration will be assessed by prescribing records and the average number of zilovertamab vedotin infusions administered will be determined.

An AE is any untoward medical occurrence in a participant administered a medicinal product; the event does not necessarily have a causal relationship with study drug administration or usage. Laboratory abnormalities, vital sign/oxygen saturation abnormalities, and adverse electrocardiogram (ECG) findings will also be recorded as AEs. A TEAE is defined as an AE that occurs or worsens in the period from the first dose of study drug administration to 30 days after the final dose of study drug administration. The number of participants with a TEAE will be reported for each arm.

A DLT is defined as a protocol pre-specified TEAE that occurs in Cycle 1 of zilovertamab vedotin therapy and is considered drug-related. Failure to recover to baseline by ≥21 days from the last dose of study drug in the current cycle due to a drug-related TEAE is also considered a DLT. The number of participants with a DLT will be reported for each arm.

An SAE is defined as an untoward medical occurrence that results in any of the following outcomes: death, life-threatening situation, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or other medically significant event.

Prespecified AESIs for this study will include: Grade ≥3 infusion reactions, tumor lysis syndrome (TLS) of any grade, and Grade ≥3 peripheral neuropathy. The number of participants with an AESI will be reported for each arm.

An AE is any untoward medical occurrence in a participant administered a medicinal product; the event does not necessarily have a causal relationship with study drug administration or usage. The number of participants that discontinue study treatment due to an AE will be reported for each arm.

The number of participants that use supportive care or concomitant medications will be reported for each arm.

Plasma concentration of zilovertamab vedotin will be reported for each arm.

Plasma concentration of total UC-961 antibody will be reported for each arm.

Plasma concentration of MMAE will be reported for each arm.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of zilovertamab vedotin.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of total UC-961 antibody.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Cmax of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Tmax of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine AUC of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine Vd of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine CL of MMAE.

Blood samples collected predose and at multiple timepoints postdose will be used to determine t1/2 of plasma concentration of MMAE.

Number of participants with zilovertamab vedotin-reactive antibodies will be assessed.

OR will be defined by achievement of the following outcomes as indicated by disease type: CLL/SLL: Complete response (CR: disappearance of detectable disease per Cheson 2012 criteria), CR with incomplete blood count recovery (CRi: CR with ≥1 additional change in absolute neutrophil count, platelet count, or hemoglobin), partial response (PR: no evidence of new disease per Cheson 2012 criteria), or PR with lymphocytosis (PR except lack of decrease in peripheral blood absolute lymphocyte count); NHL: CR (disappearance of all detectable disease per Cheson 2014 criteria) or PR (≥50% decrease in the sum of the product of diameters of the index nodal and extranodal lesions); LPL/WM: CR, very good PR (CR with ≥90% decrease in M protein), PR, or minor response (criteria for PR or stable disease met per Cheson 2014); ALL: (CR, CRi, unconfirmed CR, or PR per National Comprehensive Cancer Network criteria); AML (CR, CRi, morphologic leukemia-free state \[MLFS\], or PR per Cheson 2003 criteria).

CRMRD- is defined as the achievement of ≤1 × 10\^-4 malignant cells in bone marrow (as assessed by flow cytometry) in a participant who meets all other criteria for CR.

Percent change in tumor dimensions is defined as the percent change from baseline in the sum of the products of the diameters (SPD) of index lesions.

TTR is defined as the interval from the start of study therapy to the first documentation of an objective response.

DOR is defined as the interval from the first documentation of objective response to the earlier of the first documentation of disease progression/relapse or death from any cause.

PFS is defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression/relapse or death from any cause.

TTF failure is defined as the interval from start of study therapy to the earliest of the first documentation of disease progression/relapse, treatment failure (for participants with ALL or AML), the permanent cessation of study drug due to an AE, or death from any cause.

OS is defined as the interval from the start of study therapy to death from any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)	NCT05458297	Chronic Lymphoc... Mantle Cell Lym... Follicular Lymp... Richter Transfo...	Zilovertamab ve... Nemtabrutinib	18 Years -	Merck Sharp & Dohme LLC
A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)	NCT03833180	Chronic Lymphoc... Mantle Cell Lym... Follicular Lymp... Marginal Zone L... Diffuse Large B... Richter Transfo... Burkitt Lymphom... Lymphoplasmacyt... T-cell Non-Hodg... Acute Lymphoid ... Acute Myeloid L... Waldenstrom Mac...	Zilovertamab ve...	18 Years -	VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
A Study of Zilovertamab Vedotin (MK-2140) (VLS-101) in Participants With Hematologic Malignancies (MK-2140-001)	NCT03833180	Chronic Lymphoc... Mantle Cell Lym... Follicular Lymp... Marginal Zone L... Diffuse Large B... Richter Transfo... Burkitt Lymphom... Lymphoplasmacyt... T-cell Non-Hodg... Acute Lymphoid ... Acute Myeloid L... Waldenstrom Mac...	Zilovertamab ve...	18 Years -	VelosBio Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)	NCT05458297	Chronic Lymphoc... Mantle Cell Lym... Follicular Lymp... Richter Transfo...	Zilovertamab ve... Nemtabrutinib	18 Years -	Merck Sharp & Dohme LLC

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