A Study of Polatuzumab Vedotin and Glofitamab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma Within 12 Months After R-CHOP

This is a multicenter, single-arm, open-label, phase 2 study designed to evaluate the efficacy and safety of polatuzumab vedotin in combination with glofitamab in patients with diffuse large B-cell lymphoma (DLBCL) who are primary refractory to first-line R-CHOP therapy or relapse within 12 months after R-CHOP therapy. Approximately 47 participants will be enrolled at approximately seven study sites in Korea, allowing for an approximately 10% dropout rate to secure 42 efficacy-evaluable participants. The planned enrollment period is approximately 24 months. Participants will be followed for at least 12 months after the end of treatment, and the total study duration is expected to be approximately 4 years. Treatment will be administered for a fixed duration of up to 12 cycles, with each cycle defined as 21 days. The treatment period consists of two parts. Part A includes Cycles 1 through 6, during which participants will receive obinutuzumab pretreatment followed by combination therapy with polatuzumab vedotin and glofitamab. Obinutuzumab 1000 mg will be administered once by intravenous infusion on Cycle 1 Day 1. Polatuzumab vedotin 1.8 mg/kg will be administered by intravenous infusion on Cycle 1 Day 2 and then on Day 1 of each cycle from Cycle 2 through Cycle 6 at 21-day intervals. Glofitamab will be administered using step-up dosing: 2.5 mg by intravenous infusion on Cycle 1 Day 8, 10 mg by intravenous infusion on Cycle 1 Day 15, and 30 mg by intravenous infusion on Day 1 of each cycle from Cycle 2 through Cycle 6. Part B includes Cycles 7 through 12, during which participants will receive glofitamab monotherapy. Glofitamab 30 mg will be administered by intravenous infusion on Day 1 of each 21-day cycle. Disease response will be assessed using PET-CT, or contrast-enhanced CT if PET-CT cannot be performed, at Week 9, Week 18, Week 36, and at the end of treatment, based on Cycle 1 Day 1. Response will be evaluated according to Lugano 2014 criteria. The primary endpoint is the complete response rate at the end of treatment, as assessed by the investigator according to Lugano 2014 criteria. Secondary endpoints include overall response rate, duration of response, progression-free survival, overall survival, duration of complete response, time to first objective response, and safety. Exploratory analyses will evaluate ctDNA-based minimal residual disease and immune cell profiling in relation to clinical response and long-term outcomes. To reduce the risk of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, risk mitigation measures including obinutuzumab pretreatment, step-up dosing of glofitamab, and premedication will be implemented according to the protocol.