Glofitamab in combination with immunochemotherapy in patients with relapsed/refractory B-cell non-Hodgkin lymphoma: Phase 1b dose-escalation study.

Glofitamab was investigated with obinutuzumab/rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (G/R-CHOP) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) who had ≥1 prior obinutuzumab/rituximab-containing therapy (NCT03467373). The primary end-point was to determine the optimal biological dose of glofitamab with R-CHOP. Using a modified continual reassessment method, glofitamab dose escalation was administered from cycle (C) 2 day (D)8 (70 μg, 1800 μg, 10 mg, 30 mg), with G/R- CHOP for 6-8 21-day cycles. The 70 and 1800 μg cohorts received fixed-dose glofitamab; the 10 and 30 mg cohorts received step-up dosing (C2D8, 2.5 mg; C2D15, 10 mg; C3D8+, 30 mg). Patients completing induction could receive glofitamab every 8 weeks for ≤2 years. Thirty-one patients with follicular lymphoma (including transformed), mantle cell lymphoma or marginal zone lymphoma received treatment. The most common adverse events (AEs) were anaemia and fatigue (each 58.1%). Grade 3/4 AEs occurred in 25 (80.6%) patients (serious AEs: 23 [74.2%]; grade 5 AEs: 4 [12.9%; mostly infections]). Sixteen (51.6%) patients experienced cytokine release syndrome (grade 1/2, n = 12 [38.7%]; grade 3/4, n = 4 [12.9%]). Complete metabolic response rate was 83.9%. Median progression-free survival was not reached after 44.2 months follow-up. Glofitamab plus G/R-CHOP showed promising benefit in relapsed/refractory B-NHL, supporting future investigation of glofitamab (2.5/10/30 mg) with R-CHOP in untreated diffuse large B-cell lymphoma.