ADC Therapeutics Announces Completion of Enrollment of Phase 3 Confirmatory Clinical Trial of ZYNLONTA® in Combination with Rituximab in 2L+ Diffuse Large B-Cell Lymphoma

LOTIS-5 Trial and ZYNLONTA - LOTIS-5 is a Phase 3 confirmatory trial evaluating ZYNLONTA in combination with rituximab for relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) [7] - The trial is randomized, open-label, two-part, and multicenter, designed to confirm accelerated approval and support potential label expansion into 2L+ DLBCL [8] - Primary endpoint is progression-free survival, with secondary endpoints including overall survival, ORR, CR rate, and duration of response [1] - Topline results for the primary endpoint analysis are expected by the end of 2025, with regulatory submission to the FDA in Q1 2026 and potential approval in late 2026 [1][9] ZYNLONTA Mechanism and Approval - ZYNLONTA is a CD19-directed antibody drug conjugate (ADC) that binds to CD19-expressing cells, internalizes, and releases a pyrrolobenzodiazepine (PBD) payload, leading to cell cycle arrest and tumor cell death [2] - ZYNLONTA received accelerated approval from the FDA in 2021 and conditional approval from the EMA for treating adult patients with r/r DLBCL after two or more lines of systemic therapy [4][7] - The approval is based on overall response rate, and continued approval may depend on verification of clinical benefit in confirmatory trials [4] Clinical Trial Results and Future Plans - In part 1 of LOTIS-5, 20 patients showed an overall response rate (ORR) of 80% and a complete response (CR) rate of 50%, with no new safety signals [8] - ZYNLONTA is also being evaluated in combination studies for other B-cell malignancies and earlier lines of therapy [6][14] - The company anticipates submitting a supplemental BLA to the FDA in Q1 2026 based on LOTIS-5 results [9] Company Overview - ADC Therapeutics is a commercial-stage global leader in antibody drug conjugates (ADCs), focusing on hematologic malignancies and solid tumors [13] - The company is based in Lausanne, Switzerland, with operations in London and New Jersey [10] - ADC Therapeutics has multiple ADCs in clinical and preclinical development, in addition to ZYNLONTA [14]