This clinical trial is for adults who have a certain type of cancer called large B-cell lymphoma (LBCL) and have not yet received treatment for it.
   
The goal of this research study is to test how well an experimental drug called glofitamab works in combination with Pola-R-CHP (a regimen of five other drugs) when compared to Pola-R-CHP alone in participants with LBCL. The five drugs in Pola-R-CHP are: polatuzumab vedotin (Pola), rituximab (R), cyclophosphamide (C), doxorubicin (H), and prednisone (P). Participants will receive either glofitamab plus Pola-R-CHP (Arm A) or Pola-R-CHP alone (Arm B) to find out which is better.
   
Glofitamab is an experimental drug, which means health authorities such as the United States Food and Drug Administration (FDA) have not approved glofitamab in combination with Pola-R-CHP for the initial treatment of LBCL.
   
Polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone are drugs that have already been approved alone and in combination by some health authorities, such as the FDA, for the treatment of different types of cancer.
   
Participants will have an equal chance of being placed in either Arm A (glofitimab plus Pola-R-CHP) or Arm B (Pola-R-CHP alone). Neither the participant nor the study doctor can choose the group the participant is assigned to.
   
Participants will receive study treatment every 21 days (3 weeks). Each 21-day period is called a “cycle,” and there will be a total of eight cycles. All participants will receive: 

• Polatuzumab vedotin, given as an intravenous (IV) infusion (into the vein), (over about 30−90 minutes), once per cycle for the first 6 cycles. 
• Rituximab, given as an intravenous (IV) infusion (into the vein) (over about 1−4 hours), once per cycle for the first 6 cycles 
• Cyclophosphamide, given as an IV infusion (into the vein) once per cycle for the first 6 cycles 
• Doxorubicin, given as an IV infusion (into the vein), once per cycle for the first 6 cycles 
• Prednisone, given as pills or as an IV infusion (into the vein), five times per cycle for the first 6 cycles

Depending on which treatment arm participants are assigned to they will also receive: 

• Arm A: Glofitamab given as an IV infusion (into the vein) (over about 2 – 4 hours), twice in Cycle 2 and one time in each of the Cycles 3 to 8. Glofitamab may be given after the planned Cycle 8 in the case of a treatment delay. 
• Arm B: Rituximab, given as an IV infusion (into the vein) (over about 1 – 4 hours), once in Cycle 7 and once in Cycle 8

Participants will have approximately 14 in-person visits over 24 weeks while they are receiving study treatment before starting the follow-up period. After the final treatment dose, the study doctor will follow up with the participant by phone call or clinic visit about every 3 months during the first two years, then every six months for the following three years or for as long as the participant agrees to it.

Total time in the study will depend on how the participant’s LBCL responds to the study treatment. This could range from one day if discontinued early, to approximately 65 months if completing the full schedule of assessments.