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)).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
223
IV infusion
Oral tablet
Alaska Oncology and Hematology ( Site 0037)
Anchorage, Alaska, United States
COMPLETEDBanner MD Anderson Cancer Center ( Site 0040)
Gilbert, Arizona, United States
RECRUITINGBanner MD Anderson Cancer Center - University Medical Center Phoenix-Medical Oncology ( Site 0036)
Phoenix, Arizona, United States
RECRUITINGUniversity of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0008)
Aurora, Colorado, United States
Percentage of Participants with MCL (Cohort C), FL (Cohort D), and CLL 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 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 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 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, and FL (Cohorts D & E)
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.
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
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.
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, and FL (Cohorts D & E)
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.
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
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.
Time frame: Up to approximately 81 months
Percentage of Participants with ≥1 AE in Participants with MCL (Cohort A), RT, and FL (Cohort E)
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.
Time frame: Up to approximately 81 months
Percentage of Participants Discontinuing from Study Therapy Due to AE in Participants with MCL (Cohort A), RT, and FL (Cohort E)
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.
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Cancer Care Specialists of Illinois ( Site 0031)
Decatur, Illinois, United States
COMPLETEDUniversity of Kansas Medical Center-Division of Hematologic Malignancies and Cellular Therapeutics ( Site 0038)
Fairway, Kansas, United States
COMPLETEDNorton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0007)
Saint Matthews, Kentucky, United States
RECRUITINGGreenebaum Comprehensive Cancer Center-Hematology & Multiple Myeloma ( Site 0010)
Baltimore, Maryland, United States
COMPLETEDTufts Medical Center ( Site 0024)
Boston, Massachusetts, United States
RECRUITINGMassachusetts General Hospital ( Site 0018)
Boston, Massachusetts, United States
ACTIVE_NOT_RECRUITING...and 99 more locations
Time frame: Up to approximately 81 months