C075 | INITIAL RESULTS FROM LOTIS-7: A PHASE 1B STUDY OF LONCASTUXIMAB TESIRINE PLUS GLOFITAMAB IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA

CONTEXT: Loncastuximab tesirine (Lonca), a CD19-targeted, antibody–drug conjugate, and glofitamab (Glofit), a CD20×CD3 bispecific engager, are FDA/EMA approved for R/R DLBCL (≥3rd line). OBJECTIVES: Primary: characterize safety/tolerability of Lonca-Glofit; identify maximum tolerated/recommended expansion dose. Secondary: evaluate antitumor effects, pharmacokinetics (PK), and anti-drug antibodies (ADAs). DESIGN: LOTIS-7 (NCT04970901; phase 1b) evaluated Lonca-Glofit in histologically confirmed R/R B-NHL after ≥1 systemic therapy. PK of Lonca/analytes were evaluated by noncompartmental analysis; ADAs, by a tiered strategy. Circulating immune cells/cytokines were assessed longitudinally. Immune phenotypes were analyzed by flow cytometry; plasma cytokines by multiplex immunoassay. INTERVENTIONS: Lonca (90, 120, and 150 μg/kg; dose escalation) and (120 and 150 μg/kg; dose expansion) Q3W for fixed duration (≤8 cycles); doses 120 and 150 μg/kg reduced to 75 μg/kg for cycles ≥3 per label. Glofit (30 mg) Q3W, step-up dosing ≤12 cycles. RESULTS: As of 17Jan2025, 31 patients received ≥1 Lonca dose (median age, 73; 16.1% HGBCL, 61.3% ≥2 prior therapies; 19.4% prior CAR-T therapy). Refractory disease: primary (45.2%) and/or last (61.3%) therapy. Most common grade ≥3 TEAE was neutropenia (32.3%). Grade 1/2 CRS (29.0%/9.7%) and ICANS (0%/6.5%); no grade ≥3. Grade 3/4 TEAEs of interest (each 3.2%): generalized edema, pericardial effusion, photosensitivity reaction, rash, sepsis, pneumonia. In the efficacy-evaluable population (n=22), ORR was 95.5%, CRR 90.9%, and median DOR was not reached. Among responders (n=21), 20 remained in CR. Lonca-Glofit vs Lonca showed comparable exposure (AUC_last) but lower C_max, with moderate-high PK variability (cycles 1/2). ADAs detected in 4.7% of patients. As of 4 Oct. 2024, T-cell margination was appreciable, circulating activated CD4+ and CD8+ T cells increased during treatment. Circulating monocytes and NK cells were modulated and showed a trend of increase. Cytokine profiles indicated immune activation; when present, IL-6 induction was relatively modest in most patients. CONCLUSIONS: Lonca-Glofit in R/R B-NHL showed a manageable/consistent safety profile and encouraging efficacy in heavily-pretreated aggressive lymphoma patients. Results suggest Lonca complements Glofit’s mechanism and provides additive efficacy.