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

Condition(s) studied

Investigational drug(s) / intervention(s)

Zilovertamab vedotin: IV infusion

Nemtabrutinib: Oral tablet

Study summary

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

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.

Eligibility

Primary outcome measure(s)

• Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL (Cohort D) with ≥1 Adverse Event (AE) — Up to approximately 81 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 percentage of participants with MCL (Cohort C), FL (Cohort D), and CLL (Cohort D) who experienced an AE will be reported.
• Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL (Cohort D) who Discontinue from Study Therapy Due to AE — Up to approximately 81 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 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.
• Percentage of Participants with MCL (Cohort C) who Experience a Dose-Limiting Toxicity (DLT) — Up to approximately 81 months
  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.
• 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) — Up to approximately 81 months
  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.
• ORR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C) — Up to approximately 81 months
  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.
• ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Investigator in Participants with CLL (Cohort D) — Up to approximately 81 months
  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.

Trial sites (109)

+ 69 more sites — see the full list on the official registry below.