ADC Therapeutics reported a stumbling block for its antibody-drug conjugate Zynlonta (loncastuximab tesirine) after Phase III results from LOTIS-5 showed higher fatal adverse events in the treatment arm. The confirmatory trial evaluated Zynlonta plus rituximab versus rituximab monotherapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). While the study met its primary endpoint for progression-free survival, overall deaths were higher in the experimental arm, and treatment-emergent Grade 5 events were reported at three times the rate compared with control. ADC’s management said key secondary efficacy endpoints, including overall survival, did not show a detrimental effect. ADC attributed the safety comparison to differences in observation timing and subsequent therapy switching, noting infections were the leading cause of deaths. The update introduces increased uncertainty around how the program will progress amid safety scrutiny from investors and regulators.