ADC Therapeutics SA has announced the completion of enrollment in LOTIS-5, the Phase 3 confirmatory trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) in combination with rituximab (Lonca-R) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL).

ZYNLONTA previously received accelerated approval for the treatment of r/r DLBCL after two or more lines of systemic therapy from the FDA in 2021.

Commenting on the development, Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics said, “This milestone for LOTIS-5 brings us a step closer to providing a potential combination treatment in the 2L+ DLBCL setting that we believe will offer competitive efficacy with favourable safety and a convenient dosing schedule, well-suited for use in patients across care settings.”

He further added, “We anticipate sharing topline results of the primary endpoint analysis by the end of 2025 once the pre-specified number of events is reached and potentially submitting our supplemental BLA to the US Food and Drug Administration (FDA) in the first quarter of 2026.”

The randomised, open?label, two?part, two?arm, multicentre study is designed to confirm accelerated approval and may support potential label expansion into 2L+ in combination with rituximab.

Twenty patients were enrolled in part 1 of a non-randomised safety run?in. As previously reported, the results showed an overall response rate (ORR) by central review of 80 percent (16/20) with a complete response (CR) rate of 50 percent (10/20) and no new safety signals.

In part 2, patients with 2L+ DLBCL are randomised 1:1 to receive fixed-dose ZYNLONTA with rituximab or rituximab?gemcitabine?oxaliplatin (R?GemOx). The primary endpoint of LOTIS-5 is progression-free survival with secondary endpoints of overall survival, ORR, CR rate and duration of response as well as frequency and severity of adverse events.

Topline results of the primary endpoint analysis are anticipated by the end of 2025 once the required number of pre-specified events is reached followed by regulatory submission to the FDA in Q1 2026 and potential approval in late 2026.