A Phase 2 interventional study of Zilovertamab vedotin and Nemtabrutinib in Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma and Follicular Lymphoma, sponsored by Merck Sharp & Dohme LLC. Active, not recruiting at 109 sites in 21 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-21.
Sponsored by Merck Sharp & Dohme LLC · Phase 2, Interventional, and Treatment
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.
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).
As of Amendment 07, Cohort D is closed to enrollment of participants with CLL and enrollment of participants into Arm 2 (zilovertamab vedotin at Dose 2 on Days 1 \& 8 of each 3 Week Cycle (Q2/3W)).
As of Amendment 09, no additional participants with RT will be enrolled in Cohort B; however, those currently enrolled will continue with study intervention treatment (if applicable) until a protocol specified discontinuation criterion is met. Cohort E will be closed, as no participants with FL have been treated in this cohort.
1,603 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 243 are open to participants now.
This study's planned enrollment of 189 is above the median of 40 across 1,325 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.
Browse Leukemia, Lymphocytic, Chronic, B-Cell studies →Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.
Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
The main inclusion criteria include, but are not limited to the following:
Inclusion Criteria:
Exclusion Criteria:
Participants will receive zilovertamab vedotin intravenous (IV) infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
Biological: Zilovertamab vedotin
Participants will receive zilovertamab vedotin IV infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
Biological: Zilovertamab vedotin
Participants will receive zilovertamab vedotin IV infusion at Dose 2 every 3 weeks (Q3W) combined with nemtabrutinib oral dose daily until disease progression or discontinuation.
Biological: Zilovertamab vedotin · Drug: Nemtabrutinib
Participants will receive either zilovertamab vedotin IV infusion Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
Biological: Zilovertamab vedotin
IV infusion
Also known as: MK-2140
Oral tablet
Also known as: MK-1026
Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL (Cohort D) with ≥1 Adverse Event (AE)
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 (Cohort C), FL (Cohort D), and CLL (Cohort D) who experienced an AE will be reported.
Time frame: Up to approximately 81 months
Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL (Cohort D) who Discontinue from Study Therapy Due to AE
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 (Cohort C), FL (Cohort D), and CLL (Cohort D) who discontinued study treatment due to an AE will be reported.
Time frame: Up to approximately 81 months
Percentage of Participants with MCL (Cohort C) who Experience a Dose-Limiting Toxicity (DLT)
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 (Cohort C) as assessed by investigator will be reported.
Time frame: Up to approximately 81 months
Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) in Participants with MCL (Cohort A), RT (Cohort B), and FL (Cohort D)
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 in Participants with MCL (Cohort A), RT (Cohort B), and FL (Cohort D) will be reported.
Time frame: Up to approximately 81 months
ORR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C)
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 in Participants with MCL (Cohort C) will be reported.
Time frame: Up to approximately 81 months
ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Investigator in Participants with CLL (Cohort D)
ORR, defined as the percentage of participants who achieve a CR or PR per iwCLL criteria as assessed by investigator in participants with CLL (Cohort D) will be reported.
Time frame: Up to approximately 81 months
Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR in Participants with MCL (Cohort A), RT (Cohort B), and FL (Cohort D)
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, in Participants with MCL (Cohort A), RT (Cohort B), and FL (Cohort D) will be reported.
Time frame: Up to approximately 81 months
DOR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C)
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, in participants with MCL (Cohort C) will be reported.
Time frame: Up to approximately 81 months
DOR per iwCLL Criteria as Assessed by Investigator in Participants with CLL (Cohort D)
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, in participants with CLL (Cohort D) will be reported.
Time frame: Up to approximately 81 months
Percentage of Participants with ≥1 AE in Participants with MCL (Cohort A) and RT (Cohort B)
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 (Cohort A) and RT (Cohort B) who experienced an AE will be reported.
Time frame: Up to approximately 81 months
Percentage of Participants Discontinuing from Study Therapy Due to AE in Participants with MCL (Cohort A) and RT (Cohort B)
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 (Cohort A) and RT (Cohort B) who discontinued study treatment due to an AE will be reported.
Time frame: Up to approximately 81 months
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