Résumé
Glofitamab is a CD20xCD3 bispecific antibody with a novel 2:1 configuration. In a phase I/II study (NCT03075696), escalating doses of glofitamab were highly active and well tolerated in patients with relapsed/refractory (R/R) B-cell lymphomas.
To present results for the pivotal phase II expansion study of glofitamab in patients with R/R diffuse large B-cell lymphoma (DLBCL) and ≥2 prior therapies.
Patients with DLBCL and ≥2 prior therapies received intravenous obinutuzumab pretreatment (1000mg) on Day (D) 1, 7 days before the first glofitamab dose. Intravenous glofitamab was administered with step-up dosing on D8 (2.5mg) and D15 (10mg) of Cycle (C) 1, and at the target dose (30mg) on D1 of C2–12 (21-day cycles). The primary endpoint was Independent Review Committee-assessed complete response (CR) rate, using Lugano 2014 criteria.
As of March 14, 2022, 154 patients had received ≥1 dose of study treatment (median age: 66 years [range: 21–90]; Ann Arbor stage III/IV: 75%). Median prior therapies received was 3 (range: 2–7; ≥3 prior therapies: 60%; prior chimeric antigen receptor [CAR] T-cell therapy: 33%). Most patients were refractory to their most recent regimen (86%). After 12.6 months’ median (range: 0–22) follow-up, overall response and CR rates were 52% and 39%, respectively. CR rates in patients with and without prior CAR T-cell therapy were 35% and 42%, respectively. At 12 months, an estimated 64% of responders and 78% of complete responders remained in response; most CRs (80%; 49/61) were ongoing at data cut-off. The projected 12-month overall survival rate was 50%. Cytokine release syndrome (CRS) occurred in 63% of patients, was primarily associated with the initial doses, and was mostly Grade 1 (47%) or Grade 2 (12%); Grade 3 (3%) and Grade 4 (1%) CRS events were uncommon. No glofitamab-related Grade 5 (fatal) adverse events (AEs) occurred. Glofitamab-related AEs leading to discontinuation were uncommon (5 patients, 3%).
Fixed-duration glofitamab induces durable CRs and has a manageable safety profile in patients with R/R DLBCL and ≥2 prior therapies, including those with prior exposure to CAR T-cell therapy. ©2022 American Society of Clinical Oncology. Reused with permission.