Glofitamab Plus Polatuzumab Vedotin Continues to Demonstrate Frequent and Durable Responses and Has a Manageable Safety Profile in Patients with ≥2L Relapsed/Refractory DLBCL, Including HGBCL, and in Patients with Prior CAR T-Cell Therapy: Updated Results from a Phase Ib/II Study

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4460-4460
• Main Authors: Hutchings, Martin, Avigdor, Abraham, Sureda Balari, Anna Maria, Terol, Maria José, Bosch, Francesc, Corradini, Paolo, Larsen, Thomas S., Rueda Dominguez, Antonio, Skarbnik, Alan, Joergensen, Judit Mészáros, Lavie, David, Gurion, Ronit, Zinzani, Pier Luigi, Pinto, Antonio, Cordoba, Raul, Bottos, Alessia, Li, Donghang, Relf, James, Filézac De L'Étang, Audrey, Sellam, Gila, Gritti, Giuseppe
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-174213

Background: Glofitamab (Glofit) is a CD20xCD3 bispecific antibody which engages and redirects T cells to eliminate B cells. Glofit monotherapy recently received FDA and EMA approval for treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 prior lines of therapy. Polatuzumab vedotin (Pola) is a CD79b-targeted antibody-drug conjugate that has a complementary mode of action to Glofit, with little toxicity overlap. In this open-label, multicenter Phase Ib/II study (NCT03533283), Glofit+Pola demonstrated durable responses and a manageable safety profile in patients with R/R DLBCL (Hutchings et al. ICML 2023). We present updated results with longer follow-up in patients with R/R DLBCL, including high-grade B-cell lymphoma (HGBCL), and in patients with prior chimeric antigen receptor (CAR) T-cell therapy. Methods: Patients receivedobinutuzumab 1000mg on Cycle (C) 1 Day (D) 1 to mitigate the risk of severe cytokine release syndrome (CRS). Pola 1.8mg/kg was given on C1D2 and D1 of C2-6 (21-day cycles). Glofit was given with step-up dosing in C1 (C1D8 2.5mg; C1D15 10mg; D1 of C2-12 10/30mg) for up to 12 cycles. The primary objective was to establish the recommended Phase II dose of Glofit when combined with Pola; this was previously identified as 30mg based on the dose-escalation phase and the NCT03075696 study (Hutchings et al. ASH 2021; Hutchings et al. J Clin Oncol 2021). Results: At the data cut-off (Jan 25, 2023), 111 patients had received ≥1 dose of study drug (safety population). The median age was 68 (range 23-82) years; 61.3% of patients were male; 50.5% had DLBCL not otherwise specified (NOS), 24.3% had HGBCL, 23.4% had transformed follicular lymphoma (trFL), and 1.8% had primary mediastinal large B-cell lymphoma (PMBCL). Most patients were refractory to their last prior therapy (71.2%). Median number of prior lines of therapy was 2 (range 1-7; 61.3% of patients had received ≥2), 24.3% had received prior CAR T-cell therapy. The overall response rate (ORR) in 109 efficacy-evaluable patients was 78.0%, with a complete metabolic response (CMR) rate of 56.0%. In patients with DLBCL NOS (n=56), ORR and CMR rate were 85.7% and 60.7%, respectively. In patients with trFL (n=26), ORR and CMR rate were 76.9% and 53.8%, respectively. In patients with HGBCL (n=25), ORR and CMR rate were 60.0% and 44.0%, respectively. The two patients with PMBCL achieved a CMR. In patients who had prior CAR T-cell therapy (n=27), ORR was 77.8% and CMR r