S220: GLOFITAMAB INDUCES DURABLE COMPLETE REMISSIONS AND HAS FAVORABLE SAFETY IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA AND ≥2 PRIOR THERAPIES: PIVOTAL PHASE II EXPANSION RESULTS (2022)

Background: Glofitamab is a T-cell engaging bispecific antibody (Ab) with a novel 2:1 configuration that confers bivalency for CD20 (B cells) and monovalency for CD3 (T cells). In a Phase I/II study (NCT03075696), escalating glofitamab doses were highly active and well tolerated in patients with relapsed/refractory (R/R) B-cell lymphomas, with obinutuzumab pretreatment (Gpt) and Cycle (C) 1 step-up dosing providing effective cytokine release syndrome (CRS) mitigation. Aims: We present pivotal Phase II expansion results in patients with R/R diffuse large B-cell lymphoma (DLBCL) and ≥2 prior therapies. Methods: All patients had DLBCL (DLBCL not otherwise specified [NOS], high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, or transformed follicular lymphoma) and had received ≥2 prior regimens, including ≥1 anti-(a) CD20 Ab and ≥1 anthracycline. Intravenous (IV) Gpt (1000mg) was given 7 days before the first glofitamab dose. IV glofitamab was then given as step-up doses on Day (D) 1 (2.5mg) and D8 (10mg) of C1 and at the target dose (30mg) on D1 of C2–12 (21-day cycles). The primary endpoint was complete response (CR) rate assessed by Independent Review Committee (IRC) using Lugano 2014 criteria. CRS was assessed using ASTCT criteria. All patients provided informed consent. Results: As of September 14, 2021, 107 patients had received ≥1 dose of study treatment (median age: 66 years [21–90]; Ann Arbor stage III–IV disease: 74%; IPI score ≥3: 54%; DLBCL NOS: 74%). Median prior therapies was 3 (2–7); 59% had ≥3 prior therapies and 35% had received prior CAR T-cells (CAR-Ts). Most patients were refractory to a prior aCD20 Ab-containing regimen (85%) and to their most recent regimen (85%). Many were refractory to their initial therapy (59%) and to prior CAR-Ts (32%). After a median follow-up of 9 months (0.1–16), overall response and CR rates by IRC were 50.0% and 35.2%, respectively. CR rates were consistent in patients with and without prior CAR-Ts (32% vs 37%). Median time to CR was 42 days (95% CI: 41–48). The majority of CRs (33/38; 87%) were ongoing at data cut. An estimated 84% of complete responders and 61% of responders remained in response at 9 months. At data cut, the projected 12-month overall survival rate was 48%, and 92% of complete responders were alive. These results are consistent with earlier Phase I data in 100 patients treated with target glofitamab doses ≥10mg (CR rate: 34%; estimated 20-month CR rate in complete responders: 72%). CRS occurred in 68% of patients, was primarily associated with the initial doses, and was mostly Grade (Gr) 1 (51%) or Gr 2 (12%); Gr 3 (3%) and Gr 4 (2%) events were uncommon. All but 2 CRS events were resolved at data cut. Glofitamab-related neurologic adverse events (AEs) potentially consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 patients (all Gr 1–2). No glofitamab-related Gr 5 (fatal) AEs occurred. Glofitamab-related AEs leading to discontinuation were uncommon (3 patients, 3%). Summary/Conclusion: Fixed-duration glofitamab induces durable complete remissions and has favorable safety in patients with R/R DLBCL and ≥2 prior therapies, including those with prior exposure to CAR-Ts. Glofitamab is a promising new therapy for patients with heavily pretreated and/or highly refractory DLBCL.