Initial Safety Run-In Results of the Phase 3 LOTIS-5 Trial for R/R DLBCL Treatment

The phase 3 LOTIS-5 trial investigates the novel combination of Loncastuximab Tesirine with Rituximab (Lonca-R) versus immunochemotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Loncastuximab tesirine is an antibody-drug conjugate targeting CD19, indicated for R/R DLBCL after at least two systemic treatments. The trial's initial safety run-in involved 20 patients, with a median age of 74.5 years, who had received a median of 1 previous therapy. The treatment regimen included Lonca 0.15 mg/kg + rituximab at 375 mg/m2 every 3 weeks for 2 cycles, followed by Lonca 0.075 mg/kg + rituximab at 375 mg/m2 Q3W for up to 6 additional cycles.

As of the data cutoff on February 28, 2022, 95% of patients experienced at least one treatment-emergent adverse event (TEAE), with 50% experiencing grade ≥3 TEAEs. Common all-grade TEAEs included rash (25%), fatigue (20%), and increased gamma-glutamyltransferase (20%). The most common grade ≥3 TEAEs were increased gamma-glutamyltransferase (15%), increased alanine aminotransferase (10%), and neutropenia (10%). The overall response rate was 75%, with 40% achieving complete response and 35% partial response.

The findings suggest that Lonca-R is safe and shows encouraging antitumor activity in R/R DLBCL patients. The randomized part of the LOTIS-5 trial began in January 2022, with recruitment ongoing.