LOTIS 2 FOLLOW‐UP ANALYSIS: UPDATED RESULTS FROM A PHASE 2 STUDY OF LONCASTUXIMAB TESIRINE IN RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA

Introduction: Patients (pts) 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 and limited treatment options. Loncastuximab tesirine (Lonca) comprises humanized anti-CD19 antibody conjugated to potent pyrrolobenzodiazepine dimer toxin. LOTIS 2 is Phase study evaluating Lonca in patients R/R DLBCL (NCT03589469). Pts being followed-up, here, we present updated efficacy safety results. Methods: This multicenter, open label, single-arm enrolled adult pts (≥18 years) pathologically defined ≥2 prior systemic treatments. received 150 µg/kg every 3 weeks (Q3W) for cycles, then 75 Q3W thereafter. The primary endpoint was overall response rate (ORR), assessed by central review. Secondary endpoints included duration of (DoR), progression free survival (PFS), (OS). ORR subgroup analyses were performed. Safety treatment-emergent adverse events (TEAEs). Follow-up 12 up years after the start treatment. Results: 145 ≥1 dose Lonca. Median age 66 (range 23–94) had median therapies 2–7). At data cut off (October 26, 2020), it ≥12 months since their first dose; continue on mean 4.6 cycles (std 4.1; range 1–22) 48.3% (complete [CR]: 24.8%; partial [PR]: 23.4%). DoR 12.6 responders (n = 70; CR PR), not reached (Figure 1). PFS 4.9 OS 9.5 months. For older (≥75 years), 52.4%. double-/triple-hit 33.3% transformed disease 44.8%. ORRs refractory first-line therapy, most recent therapy all 37.9%, 36.9%, 36.0%, respectively. Following treatment, 15 CD19-directed chimeric antigen receptor T-cell an investigator-assessed 46.7%, 11 proceeded SCT as consolidation responding common (≥25.0%) all-grade TEAEs increased gamma-glutamyltransferase (GGT) (41.4%), neutropenia (40.0%), thrombocytopenia (33.1%), fatigue (27.6%), anemia (26.2%). Grade ≥3 reported 107 (73.8%) pts. Treatment-related leading discontinuation delays 26 (17.9%) 62 (42.8%) pts, respectively; reason both GGT (16 [11.0%] [17.9%], respectively). Conclusions: After longer follow-up 2, durable responses be observed heavily pre-treated DLBCL. No new concerns reported. best research funded by: ADC Therapeutics SA Keywords: Aggressive non-Hodgkin lymphoma, Immunotherapy Conflicts interests pertinent abstract P. L. Zinzani Consultant advisory role: Verastem, MSD, Eusapharma, Sanofi, Therapeutics, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, Roche, Kyowa Kirin, Takeda, TG F. Caimi Kite Genentech, Amgen, Bayer, Celgene Research funding: C. Carlo-Stella Boehringer Ingelheim, Novartis, Genenta Science srl, Karyopharm Honoraria: Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca Rhizen Pharmaceuticals W. Ai Nurix, Kymera Nurix J. Alderuccio Puma Biotechnology, Inovio Pharmaceuticals, Agios Forma Foundation Medicine (immediate family member). (Self) Other remuneration: OncLive OncInfo (paid expert testimony) K. M. Ardeshna Celgene, Beigene Supported University College London (UCL)/UCL Hospitals Biomedical Unit B. Hess S. Kahl Roche Radford Bristol Myers Pharma, Seattle Genetics Stock ownership: GlaxoSmithKline (Spouse) Takeda Solh A. Stathis Pfizer, Merck, MEI-Pharma, Abbvie, PharmaMar Feingold Employment leadership position: D. Ungar Y. Qin He Hamadani R&D, Incyte Corporation, Pharmacyclics, Omeros, AbGenomics, TeneoBio, Sanofi Genzyme, Pharmaceutical, Spectrum Astellas Pharma