Phase I study of glofitamab in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma

BACKGROUND: Glofitamab is a T-cell engaging CD20xCD3 bispecific antibody approved for treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in the US and Europe. METHODS: This phase I study (jRCT2080225077) investigated safety, pharmacokinetics, and efficacy of glofitamab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Patients received obinutuzumab pretreatment (1000 mg) 7 days before first glofitamab administration. Glofitamab was given with step-up dosing on Cycle (C)1 Day (D)1 and D8, then at target dose every 3 weeks from C2D1 (7 days after C1D8) (Cohort 1: 2.5/10/16 mg; Cohort 2: 2.5/10/30 mg) until progression. Primary endpoints were safety and pharmacokinetics; secondary endpoint was efficacy. RESULTS: Eight patients with B-NHL (DLBCL, n = 5; follicular lymphoma [FL], n = 2; transformed FL, n = 1) were enrolled (Cohort 1, n = 5; Cohort 2, n = 3; median age, 64.5 years; Ann Arbor Stage III/IV, n = 7). The two patients with FL received no glofitamab due to hematological adverse events (AEs) after obinutuzumab. Median number of glofitamab cycles was 48 (Cohort 1) and 43 (Cohort 2). Seven patients had grade 3/4 AEs; no grade 5 AEs were reported. Two patients had serious AEs; no dose-limiting toxicities were observed. Cytokine release syndrome occurred in all glofitamab-treated patients (grade 1/2/3: n = 3/n = 2/n = 1), predominantly in C1. Serum glofitamab concentrations showed similar time profiles in both cohorts, and exposure increased in a dose-proportional manner. Overall and complete response rates were 75.0% (6/8 patients; Cohort 1: 3/5 patients [60.0%]; Cohort 2: 3/3 patients [100%]). CONCLUSION: Glofitamab demonstrated a manageable safety profile with encouraging response rates in Japanese patients with relapsed/refractory B-NHL.