A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination With Nemtabrutinib (MK-1026) in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination with nemtabrutinib 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 nemtabrutinib with respect to objective response rate.
-
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
-
RT: relapsed or refractory disease after at least 1 prior systemic therapy
-
MCL: relapsed or refractory disease after at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi
-
FL and CLL: relapsed or refractory disease 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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Zilovertamab vedotin 2.5 mg/kg Participants will receive zilovertamab vedotin 2.5 mg/kg every 3 weeks (Q3W) until disease progression or discontinuation. Participants who have MCL will receive nemtabrutinib until disease progression or discontinuation. |
Biological: Zilovertamab vedotin
IV infusion
Other Names:
Drug: Nemtabrutinib
65 to 80 mg once daily (QD) orally
Other Names:
|
| Experimental: Zilovertamab vedotin 2.0 mg/kg Participants will receive zilovertamab vedotin 2.0 mg/kg repeated 3-week cycles with drug infusions on Days 1 and 8 of each cycle (Q2/3W) until disease progression or discontinuation. |
Biological: Zilovertamab vedotin
IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants with ≥1 Adverse Event (AE) [MCL, FL, and CLL] [Up to approximately 57 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, FL, and CLL who experienced an AE will be reported.
- Percentage of Participants Discontinuing from Study Therapy Due to AE (MCL, FL, and CLL) [Up to approximately 57 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, FL, and CLL who discontinued study treatment due to an AE will be reported.
- Percentage of Participants with Dose-Limiting Toxicity (DLT) [Up to approximately 57 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 as assessed by investigator will be reported.
- Objective Response Rate (ORR) per Lugano Response Criteria as Assessed by Blinded Independent Central Review (BICR) [Up to approximately 57 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 will be reported.
- ORR per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Investigator [Up to approximately 57 months]
ORR, defined as the percentage of participants who achieve a CR or PR per iwCLL criteria as assessed by investigator will be reported.
Secondary Outcome Measures
- Duration of Response (DOR) per Lugano Response Criteria as Assessed by BICR [Up to approximately 57 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, will be reported.
- DOR per iwCLL Criteria as Assessed by Investigator [Up to approximately 57 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, will be reported.
- Percentage of Participants with ≥1 AE (MCL, RTL, FL, and CLL) [Up to approximately 57 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, RTL, FL, and CLL who experienced an AE will be reported.
- Percentage of Participants Discontinuing from Study Therapy Due to AE (MCL, RTL, FL, and CLL) [Up to approximately 57 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, RTL, FL, and CLL who discontinued study treatment due to an AE will be reported.
Eligibility Criteria
Criteria
The main inclusion criteria include, but are not limited to the following:
Inclusion Criteria:
-
For aggressive B-cell malignancies MCL and 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 FL and 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 ECOG performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.
Exclusion Criteria:
-
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, including investigational agents, within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (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.
-
Active HBV or hepatitis C virus (HCV) infection.
-
For MCL, has any clinically significant gastrointestinal abnormalities that might alter absorption.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical Oncology Associates, PS ( Site 0005) | Spokane | Washington | United States | 99208 |
| 2 | Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca-Hematology ( S | Salamanca | Spain | 37007 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2140-006
- MK-2140-006
- 2021-004450-36