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.
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Part I and II: Percentage of Participants With Dose Limiting Toxicities (DLTs)
Timeframe: From Baseline up to 4 weeks
Part I, II and III: Percentage of Participants With Adverse Events (AEs)
Timeframe: 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
Timeframe: From Baseline up to 4 weeks
Part II: Recommended Phase II Dose (RP2D) of Glofitamab
Timeframe: 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)
Timeframe: From treatment start up to 5 years
Part I, II and III: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab
Timeframe: At pre-defined intervals from Cycle 1 Day 1 to Day 71
Part I, II and III: Maximum Serum Concentration (Cmax) of Glofitamab
Timeframe: At pre-defined intervals from Cycle 1 Day 1 to Day 198
Part I, II and III: Minimum Serum Concentration (Cmin) of Glofitamab
Timeframe: At pre-defined intervals from Cycle 1 Day 1 up to Day 198
Part I, II and III: Clearance (CL) of Glofitamab
Timeframe: 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
Timeframe: At pre-defined intervals from Cycle 1 Day 1 to Day 71
Part I, II and III: Half-life (t1/2) of Glofitamab
Timeframe: At pre-defined intervals from Cycle 1 Day 1 to Day 71