The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in combination with standard of care options for the treatment of rrDLBCL. This study will be divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx with respect to progression-free survival (PFS) per Lugano response criteria by blinded independent review committee (BICR); and that ZV in combination with bendamustine rituximab (BR) is superior to BR with respect to PFS per Lugano response criteria by BICR. With protocol amendment 4 (effective: 04-April-2024), enrollment in Cohort B (study arms Bendamustine Rituximab \[BR\] and ZV + BR) is discontinued. No efficacy outcome analysis and hypothesis testing will be conducted for Cohort B.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
290
Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg
IV Infusion 375 mg/m\^2
IV Infusion 1000 mg/m\^2
IV Infusion 100 mg/m\^2
IV Infusion 90 mg/m\^2
Prophylactic G-CSF will be administered at each cycle of zilovertamab vedotin as per the institutional guidelines.
Palo Verde Hematology/ Oncology Center, Ltd. ( Site 0175)
Glendale, Arizona, United States
RECRUITINGBeverly Hills Cancer Center ( Site 0184)
Beverly Hills, California, United States
ACTIVE_NOT_RECRUITINGBass Medical Group ( Site 0166)
Walnut Creek, California, United States
RECRUITINGInnovative Clinical Research Institute ( Site 0122)
Whittier, California, United States
Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1
The CTCAE, Version 5.0 will be used to grade the severity of AEs in this study. DLTs will be reported for Part 1 of this study.
Time frame: Up to ~6 weeks
Number of participants who experienced an adverse event (AE)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE will be reported.
Time frame: Up to ~68 months
Number of participants who discontinued study treatment due to an AE
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued study treatment due to an AE will be reported.
Time frame: Up to ~68 months
Overall survival (OS)
OS, defined as the time from randomization to death due to any cause will be reported.
Time frame: Up to ~35 months
Progression-free survival (PFS)
PFS, defined as the time from randomization to the first documented disease progression per Lugano response criteria as assessed by BICR or death due to any cause, whichever occurs first will be presented.
Time frame: Up to ~35 months
Objective response rate (ORR)
ORR, defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per Lugano criteria as assessed by BICR will be presented.
Time frame: Up to ~35 months
Duration of response (DOR)
DOR, defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first, will be reported.
Time frame: Up to ~35 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0163)
Boca Raton, Florida, United States
RECRUITINGClermont Oncology Center ( Site 0174)
Clermont, Florida, United States
RECRUITINGBRP-Hialeah Hospital ( Site 0182)
Hialeah, Florida, United States
RECRUITINGIllinois Cancer Specialists ( Site 8000)
Niles, Illinois, United States
RECRUITINGSaint Elizabeth Medical Center Edgewood ( Site 0165)
Edgewood, Kentucky, United States
RECRUITINGUniversity of Kentucky Chandler Medical Center ( Site 0158)
Lexington, Kentucky, United States
ACTIVE_NOT_RECRUITING...and 125 more locations