A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)
- Conditions
- Mantle Cell LymphomaRichter Transformation LymphomaChronic Lymphocytic LeukemiaFollicular Lymphoma
- Interventions
- Registration Number
- NCT05458297
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief 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)).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 223
- For aggressive B-cell malignancies mantle cell lymphoma (MCL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor(s) (BTKi), and is post chimeric antigen receptor T (CAR-T) cell therapy or is ineligible for CAR-T cell therapy.
- For aggressive B-cell malignancies MCL Cohort C: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi.
- For aggressive B-cell malignancies Richter transformation lymphoma (RTL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease.
- For indolent B-cell malignancies follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL): Has histologically confirmed biopsy and has relapsed or refractory disease after at least 2 prior systemic therapies and no other available therapy.
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization/allocation.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.
- Has received solid organ transplant at any time.
- 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 (<6 months prior to enrollment), 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.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Participants with FL who have transformed to a more aggressive type of lymphoma.
- Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (if prior therapy was small molecules like kinase inhibitors) prior to the first dose of study intervention.
- Has received prior radiotherapy within 28 days of start of study intervention. Participants must have recovered from all radiation-related toxicities.
- 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 known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection not well controlled on antiretroviral therapy (ART)
- Active HBV or hepatitis C virus (HCV) infection.
- For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A, Relapsed or Refractory MCL with 2 Prior Lines of Therapy Zilovertamab vedotin Participants will receive zilovertamab vedotin intravenous (IV) infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation. Cohort B, Relapsed or Refractory RT with 1 Prior Line of Therapy Zilovertamab vedotin Participants will receive zilovertamab vedotin IV infusion at Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation. Cohort C, Relapsed or Refractory MCL with 1 Prior Line of Therapy 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. Cohort C, Relapsed or Refractory MCL with 1 Prior Line of Therapy Nemtabrutinib 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. Cohort D, Relapsed or Refractory FL and CLL with 2 Prior Lines of Therapy Zilovertamab vedotin Participants will receive either zilovertamab vedotin IV infusion Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation. Cohort E, Relapsed or Refractory FL with 2 Prior Lines of Therapy Zilovertamab vedotin Participants will receive either zilovertamab vedotin IV infuison Dose 1 every 3 weeks (Q3W) until disease progression or discontinuation.
- Primary Outcome Measures
Name Time Method Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL 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 who experienced an AE will be reported.
Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL 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 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, and FL (Cohorts D & E) 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, and FL (Cohorts D \& E) 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 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 will be reported.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR in Participants with MCL (Cohort A), RT, and FL (Cohorts D & E) Up to approximately 81 months 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, and FL (Cohorts D \& E) will be reported.
DOR per Lugano Response Criteria as Assessed by Investigator in Participants with MCL (Cohort C) Up to approximately 81 months 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.
DOR per iwCLL Criteria as Assessed by Investigator in Participants with CLL Up to approximately 81 months 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 will be reported.
Percentage of Participants with ≥1 AE in Participants with MCL (Cohort A), RT, and FL (Cohort E) 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 A), RTL, and FL (Cohort E) who experienced an AE will be reported.
Percentage of Participants Discontinuing from Study Therapy Due to AE in Participants with MCL (Cohort A), RT, and FL (Cohort E) 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 A), RT, and FL (Cohort E) who discontinued study treatment due to an AE will be reported.
Trial Locations
- Locations (109)
Alaska Oncology and Hematology ( Site 0037)
🇺🇸Anchorage, Alaska, United States
Banner MD Anderson Cancer Center ( Site 0040)
🇺🇸Gilbert, Arizona, United States
Banner MD Anderson Cancer Center - University Medical Center Phoenix-Medical Oncology ( Site 0036)
🇺🇸Phoenix, Arizona, United States
University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0008)
🇺🇸Aurora, Colorado, United States
Cancer Care Specialists of Illinois ( Site 0031)
🇺🇸Decatur, Illinois, United States
University of Kansas Medical Center-Division of Hematologic Malignancies and Cellular Therapeutics ( Site 0038)
🇺🇸Fairway, Kansas, United States
Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0007)
🇺🇸Saint Matthews, Kentucky, United States
Greenebaum Comprehensive Cancer Center-Hematology & Multiple Myeloma ( Site 0010)
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center ( Site 0024)
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital ( Site 0018)
🇺🇸Boston, Massachusetts, United States
Scroll for more (99 remaining)Alaska Oncology and Hematology ( Site 0037)🇺🇸Anchorage, Alaska, United StatesStudy CoordinatorContact888-577-8839