LOTIS-2 follow-up analysis: updated results from a phase 2 study of loncastuximab tesirine (Lonca) in relapsed or refractory diffuse large B-cell lymphoma

Abstract

Context: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who are ineligible for, or relapse after, salvage chemotherapy/stem cell transplant (SCT) have a poor prognosis. Lonca comprises a humanized anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer toxin. Objective:To assess updated effi cacy and safety fi ndings from a Phase 2 study evaluating Lonca in patients with R/R DLBCL (LOTIS-2; NCT03589469). Design: Multicenter, open-label, single-arm Phase 2 study in adult patients (≥18 years) with pathologically defined R/R DLBCL and ≥2 prior systemic treatments. Intervention: Lonca (150 µg/kg every 3 weeks [Q3W] for 2 cycles; 75 µg/kg Q3W thereafter). Main Outcomes Measures: Primary effi cacy endpoint: Overall response rate (ORR), assessed by central review. Secondary effi cacy endpoints: Duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Safety analyses: Treatment-emergent adverse events (TEAEs). Follow-up period: Q12W for up to 3 years after end of treatment. Results: 145 patients with R/R DLBCL received ≥1 Lonca dose. Median age was 66 years (range 23–94). Patients received a median of 3 prior therapies (range 2–7). At data cut-off (October 26, 2020, 12 months since first dose), 2 patients continued treatment. Patients received a mean of 4.6 Lonca cycles (std 4.1; range 1–22). ORR was 48.3% (complete response [CR]: 24.8%; partial response [PR]: 23.4%). Median DoR was 12.6 months for patients with CR or PR (n=70); not reached for patients with CR. Median PFS and OS were 4.9 and 9.5 months, respectively. Post-Lonca treatment, 15 patients received CD19-directed chimeric antigen receptor T-cell therapy with an investigator-assessed ORR of 46.7%, and 11 patients proceeded to SCT as consolidation after Lonca response. Most common (≥25.0%) all-grade TEAEs were increased gamma-glutamyltransferase (41.4%), neutropenia (40.0%), thrombocytopenia (33.1%), fatigue (27.6%), and anemia (26.2%). Grade 3 TEAEs occurred in 107 (73.8%) patients. Treatment-related TEAEs leading to treatment discontinuation and dose delays occurred in 26 (17.9%) and 62 (42.8%) patients, respectively. Conclusions: After longer follow-up of patients in LOTIS-2, durable responses to Lonca continue to be observed in heavily pre-treated patients with R/R DLBCL. No new safety concerns occurred. Research funding: ADC Therapeutics SA. Keywords: non-Hodgkin lymphoma, diffuse large B-cell lymphoma, antibody-drug conjugate, loncastuximab tesirine, Phase 2