This is a phase 1B, multi-center, dose-finding study of glofitamab administered in combination with obinutuzumab (Gazyva; \[G\]), rituximab (R) and standard doses of CHOP (G/R-CHOP or R-CHOP) in participants with r/r NHL and G/R CHOP or Pola-R-CHP in participants with untreated diffuse large B-cell lymphoma (DLBCL). Evaluating the safety, preliminary activity, pharmacokinetic (PK), and pharmacodynamic effects of this combination will be the main objectives of this study. The study is divided in two parts: * Part I: Dose finding in participants with r/r NHL; test use of G vs R in Cycle 1 * Part II: Dose Expansion. The maximum tolerated dose or optimal biological dose (MTD or OBD) will be further assessed in participants with untreated DLBCL (\>18 years of age with an age-adjusted International Prognostic Index (IPI) of 2-5). Glofitamab will be studied in combination with R-CHOP and Pola-R-CHP.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
111
Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.
Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only
Rituximab will be administered as an IV infusion at a dose of 375 mg/m\^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).
Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.
Cyclophosphamide 750 mg/m\^2 administered IV on Day 1 of each 21-day cycle
Doxorubicin 50 mg/m\^2 administered IV on Day 1 of each 21-day cycle
Vincristine 1.4 mg/m\^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg
Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle
Polatuzumab vedotin 1.8 mg/kg administered IV on Day 1 of each 21-day cycle
University of Alabama Medical Center
Birmingham, Alabama, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Fox Chase-Temple Cancer Center
Philadelphia, Pennsylvania, United States
Peter Maccallum Cancer Centre
Melbourne, Victoria, Australia
Princess Margaret Cancer Center
Toronto, Ontario, Canada
Rigshospitalet
København Ø, Denmark
Hopital Claude Huriez
Lille, France
Hopital Hotel Dieu Et Hme
Nantes, France
Centre Henri Becquerel
Rouen, France
Universitätsklinikum Erlangen, Translational Research Center (TRC), Medizin 5
Erlangen, Germany
...and 12 more locations
Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs)
Time frame: Up to 29 months
Part I and II: Percentage of Participants with Adverse Events
Time frame: Up to 29 months
Parts I and II: Percentage of Participants with a Complete Response (CR) as Assessed by the Investigator using Modified Lugano 2014 Criteria
Time frame: Up to 29 months
Parts I and II: Percentage of Participants with Overall Response (Partial Response [PR] or Complete Response [CR])
Time frame: Up to 29 months
Parts I and II: Duration of Response (DOR)
Time frame: Up to 29 months
Duration of CR
Time frame: Up to 29 months
Progression-Free Survival (PFS)
Time frame: Up to 29 months
Overall Survival (OS)
Time frame: Up to 29 months
Time to First Complete Response (TFCR)
Time frame: Up to 29 months
Time to First Response (TFOR)
Time frame: Up to 29 months
Parts I and II: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab
Time frame: Cycle 1 Day 1 up to 29 months
Parts I and II: Time to Maximum Serum Concentration (tmax) of Glofitamab
Time frame: Cycle 1 Day 1 up to 29 months
Parts I and II: Maximum Serum Concentration (Cmax) of Glofitamab
Time frame: Cycle 1 Day 1 up to 29 months
Parts I and II: Minimum Serum Concentration (Cmin) of Glofitamab
Time frame: Cycle 1 Day 1 up to 29 months
Change from Baseline in T-cell Activation Markers
Time frame: Up to 29 months
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