This is a Phase I/II, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel T-Cell bispecific (TCB), glofitamab, administered by intravenous (IV) infusion as a single agent and in combination with obinutuzumab, following pre-treatment with a one-time, fixed dose of obinutuzumab. This entry-into-human (EIH) study is divided in 3 parts: dose escalation (Parts I and II) and dose expansion (Part III). Single-participant dose-escalation cohorts will be used in Part I, followed by conversion to multiple participant dose-escalation cohorts (Part II), in order to define a tentative maximum tolerated dose (MTD) or optimal biological dose (OBD). The expansion cohorts (Part III) will be initiated when the tentative MTD/OBD is defined, to further evaluate the safety, PK and therapeutic activity of glofitamab.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
940
Glofitamab will be administered at a dose and as per the schedule specified in the respective arms.
Obinutuzumab 1000 mg single dose IV infusion on Day -7; or 2000 mg single dose administered on Day -7, or split into two 1000 mg doses administered on Days -1 and -7, and per the schedule specified in the respective arms.
Tocilizumab will be administered as an IV infusion, if required, for the management of severe Cytokine Release Syndrome (CRS) occurring during or after any infusion of glofitamab, as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents.
University of Michigan
Ann Arbor, Michigan, United States
Washington University
St Louis, Missouri, United States
Mount Sinai Medical Center
New York, New York, United States
MSKCC
New York, New York, United States
Allegheny Health Network (Pittsburg PA)
Pittsburgh, Pennsylvania, United States
Part I and II: Percentage of Participants With Dose Limiting Toxicities (DLTs)
Time frame: From Baseline up to 4 weeks
Part I, II and III: Percentage of Participants With Adverse Events (AEs)
Time frame: From Baseline up to 90 days after last dose of study drug or until study completion or participant withdrawal (up to 5 years)
Part II: MTD or OBD of Glofitamab
Time frame: From Baseline up to 4 weeks
Part II: Recommended Phase II Dose (RP2D) of Glofitamab
Time frame: From Baseline up to 5 years
Part III: Complete Response (CR) Rate as Assessed by Independent Review Committee (IRC) According to Standard Non-hodgkin's Lymphoma (NHL) Response Criteria (Lugano Classification)
Time frame: From treatment start up to 5 years
Part I, II and III: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab
Time frame: At pre-defined intervals from Cycle 1 Day 1 to Day 71
Part I, II and III: Maximum Serum Concentration (Cmax) of Glofitamab
Time frame: At pre-defined intervals from Cycle 1 Day 1 to Day 198
Part I, II and III: Minimum Serum Concentration (Cmin) of Glofitamab
Time frame: At pre-defined intervals from Cycle 1 Day 1 up to Day 198
Part I, II and III: Clearance (CL) of Glofitamab
Time frame: At pre-defined intervals from Cycle 1 Day 1 to Day 71
Part I, II and III: Volume of Distribution at Steady-state (Vss) of Glofitamab
Time frame: At pre-defined intervals from Cycle 1 Day 1 to Day 71
Part I, II and III: Half-life (t1/2) of Glofitamab
Time frame: At pre-defined intervals from Cycle 1 Day 1 to Day 71
Part I, II and III: Cmax of Obinutuzumab
Time frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of Cycle 1
Part I, II and III: Cmin of Obinutuzumab
Time frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of Cycle 1
Part I, II and III: Anti-drug Antibodies (ADA) to Glofitamab
Time frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of glofitamab on Day 1 of each cycle from Cycle 2 onwards for a maximum of 8-12 cycles, and at EOT/follow-up visit (up to 5 years)
Parts I and II: Percentage of Participants With Overall Response (Partial Response [PR] or Complete Response [CR]) as Determined by the Lugano Classification
Time frame: From Baseline up to end of study or discontinuation due to disease progression (up to 5 years)
Part I, II and III: Percentage of Participants With PR or CR (Overall Response Rate [ORR]) as Determined by the Lugano Classifications
Time frame: From Baseline up to end of study or discontinuation due to disease progression (up to 5 years)
Part I, II and III: Duration of Response (DOR) as Determined by the Lugano Classification
Time frame: From first occurrence of documented objective response until disease progression, relapse or death due to any cause (up to 5 years)
Part I, II and III: Duration of Complete Response (DOCR) as Determined by the Lugano Classification
Time frame: From the first occurrence of a documented, complete response, until the time of relapse or death from any cause (up to 5 years)
Part I, II and III: Progression-Free Survival (PFS) as Determined by the Lugano Classification
Time frame: From first study treatment to the first occurrence of disease progression or death due to any cause (up to 5 years)
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Swedish Cancer Inst.
Seattle, Washington, United States
Prince of Wales Hospital
Randwick, New South Wales, Australia
Peter Maccallum Cancer Centre
Melbourne, Victoria, Australia
Cliniques Universitaires St-Luc
Brussels, Belgium
UZ Gent
Ghent, Belgium
...and 24 more locations
Overall Survival (OS)
Time frame: From the time of first study treatment to death from any cause (up to 5 years)
Time to First Overall Response (TFOR)
Time frame: From time of treatment start to first documented response (up to 5 years)
Time to First Complete Response (TFCR)
Time frame: From treatment start to first documented complete response (up to 5 years)
Part III: Health Related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30)
Time frame: From baseline through follow-up or until disease progression (up to 5 years)
Part III: HRQoL as Assessed by the Functional Assessment of Cancer Therapy-lymphoma (FACT-lym) Scale
Time frame: From baseline through follow-up or until disease progression (up to 5 years)