ADC Therapeutics reported a stumbling block for Zynlonta (loncastuximab tesirine) after Phase 3 results from LOTIS-5 showed higher fatal adverse events in the treatment arm. The antibody-drug conjugate combined with rituximab met the primary endpoint for progression-free survival versus rituximab alone, but overall deaths and Grade 5 treatment-emergent adverse events were elevated. ADC said overall survival did not show a detrimental effect on its key secondary efficacy endpoint, and it attributed part of the observed death-rate pattern to differences in observation windows and subsequent therapy switching. Still, infections were the leading cause of deaths and were higher in the test arm than in the control. Investors pointed to the magnitude of the Grade 5 TEAE imbalance versus the company’s earlier Phase 2 LOTIS-2 study, raising questions about risk management and future trial strategy. For the ADC space, the report is a reminder that confirmatory programs can expose safety liabilities even when efficacy endpoints are achieved, and that comparative mortality effects can reshape regulatory and commercial trajectories.