ADC Therapeutics’ Zynlonta (loncastuximab tesirine) hit a major clinical snag after confirmatory Phase III results for LOTIS-5 showed higher fatality rates in the treatment arm. The study met its primary endpoint on progression-free survival in relapsed or refractory diffuse large B-cell lymphoma when combined with rituximab. However, ADC said overall deaths were higher in the Zynlonta arm versus rituximab monotherapy, with Grade 5 treatment-emergent adverse events three times higher. The company reported that no detrimental effect was observed on overall survival as a key secondary endpoint, and it attributed part of the death-rate signal to differing treatment switching windows. Infections emerged as the dominant cause of fatalities, with company leadership pointing to hepatotoxicity and edema/effusion also occurring more frequently in the test arm. Investors contrasted the Grade 5 TEAE profile with prior LOTIS-2 Phase II outcomes.