This study consists of a dose escalation/confirmation phase and an efficacy expansion phase. The dose escalation/confirmation phase is to determine the safety and tolerability and establish a preliminary recommended Phase 2 dose (RP2D) of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease. The efficacy expansion phase is to determine the efficacy of the RP2D of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
IV or oral administration (per local guidelines)
IV or oral administration (per local guidelines)
BC Cancer Victoria-Clinical Trials Unit ( Site 0105)
Victoria, British Columbia, Canada
William Osler Health System ( Site 0106)
Toronto, Ontario, Canada
Hopital du Sacre-Coeur de Montreal ( Site 0108)
Montreal, Quebec, Canada
Hadassah Medical Center ( Site 0401)
Jerusalem, Israel
Sheba Medical Center-Hemato Oncology ( Site 0400)
Ramat Gan, Israel
Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) in Cycle 1
DLTs will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and are defined as any drug-related adverse event (AE) observed during the DLT evaluation period (e.g. Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle. The number of participants with DLTs in Cycle 1 will be reported.
Time frame: Cycle 1 (up to 21 days)
Number of Participants Who Experienced At Least One 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 number of participants who experience an AE will be reported.
Time frame: Up to approximately 8 months
Number of Participants Who Discontinued Study Treatment Due to an 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 number of participants who discontinue study treatment due to an AE will be reported.
Time frame: Up to approximately 5.5 months
Complete Response Rate (CRR) per Lugano Response Criteria
CRR is defined as the percentage of participants who achieve a Complete Response (CR) per Lugano response criteria \[Cheson, B. D., et al 2014\] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with computed tomography (CT) or magnetic resonance imaging (MRI), metabolic imaging with positron emission tomography (PET), and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with CRR will be reported.
Time frame: Up to approximately 60 months
Objective Response Rate (ORR) per Lugano Response Criteria
ORR is defined as the percentage of participants who achieve a CR or PR per Lugano response criteria \[Cheson, B. D., et al 2014\] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with CT or MRI, metabolic imaging with PET, and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with ORR will be reported.
Time frame: Up to approximately 60 months
Duration of Response (DOR) per Lugano Response Criteria
For participants who demonstrate a confirmed CR or PR per Lugano response criteria \[Cheson, B. D., et al 2014\] for malignant lymphoma, DOR is 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. CR and PR assessment includes anatomic imaging with CT or MRI, metabolic imaging with PET, and clinical findings including physical examination and bone marrow biopsy results. DOR as assessed by the investigator will be reported.
Time frame: Up to approximately 60 months
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Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 0306)
Rome, Lazio, Italy
Ospedale San Raffaele-Unità Linfomi ( Site 0305)
Milan, Lombardy, Italy
Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0307)
Palermo, Sicily, Italy
Azienda Ospedaliera Universitaria Careggi-SOD Ematologia ( Site 0308)
Florence, Tuscany, Italy
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant
Alessandria, Italy
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