ABCL-360: Glofitamab Step-Up Dosing (SUD): Updated Efficacy Data Show High Complete Response Rates in Heavily Pretreated Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma (NHL) Patients (Pts)

Context Glofitamab, a T-cell-engaging, bispecific, full-length antibody, allows bivalent binding to CD20 (B-cells) and monovalent binding to CD3 (T-cells). In NP30179 (NCT03075696), an ongoing multicenter, phase I, dose-escalation and expansion study, glofitamab SUD, in addition to Gpt, allowed dose escalation ≤30 mg to maximize efficacy while mitigating cytokine release syndrome (CRS) (Hutchings et al. J Clin Oncol 2021). Objective To present updated efficacy data from glofitamab monotherapy SUD cohorts. Methods Gpt (1000 mg) was given 7 days pre-glofitamab initial dose. Intravenous glofitamab SUD was given on day (D) 1 and 8 of cycle (C) 1, then at target dose from C2D1 (2.5/10/16 mg or 2.5/10/30 mg); treatment continued for ≤12 cycles, every 21 days. Response rates were based on the Lugano criteria (Cheson et al. J Clin Oncol 2014). Results As of December 1, 2020, 52 pts received glofitamab SUD; 17 and 35 pts received 2.5/10/16 mg and 2.5/10/30 mg, respectively. Twenty-eight pts (53.8%) had aggressive NHL (aNHL) and 24 pts had indolent NHL (iNHL). Median age: 68 (44–85) years; median 3 (1–12) prior lines of therapy; 40 (76.9%) and 38 (73.1%) pts were refractory to their most recent and any prior CD20 therapy, respectively. Median follow-up duration: 6.3 months. Best overall response (OR) and complete metabolic response (CMR) rates for aNHL cohort: 64.3% and 57.1%, respectively. 4/5 pts (80%) with mantle cell lymphoma (2.5/10/16 mg, n=2; 2.5/10/30 mg, n=2) had CMR. For aNHL, 13/16 CMRs are ongoing, with 8 CMRs lasting >3 months. OR and CMR rates for pts with iNHL: 79.2% and 70.8%, respectively, with 14/17 CMRs ongoing and 10 CMRs lasting >3 months. As of August 3, 2020, common adverse events were CRS (63.5%), neutropenia (38.5%), and pyrexia (32.7%), with CRS mostly confined to C1. Grade (Gr) 1 and 2 CRS was reported in 18 (34.6%) and 12 (23%) pts, respectively; 3 pts had Gr 3 CRS; none had Gr 4/5 events (defined by ASTCT 2019 criteria). Conclusions Updated data for glofitamab monotherapy SUD show higher preliminary response rates than previously reported in pts with R/R NHL who have failed multiple lines of therapy. CRS was mostly manageable, low-grade, and confined to C1.