Stopped Early

ADC Therapeutics halts hepatic-impairment PK study of Zynlonta at 5 patients

LOTIS-10 closed after enrolling only 5 of a planned 56 patients, with ADC Therapeutics citing regulatory interactions and enrollment challenges rather than safety findings.

ADC Therapeutics terminated LOTIS-10, a Phase 1 pharmacokinetics and safety study of loncastuximab tesirine (Zynlonta) in relapsed or refractory DLBCL patients with hepatic impairment, after enrolling 5 of a targeted 56 participants.

By AppliedXLJuly 20, 2026Trial NCT05660395

Executive Summary

ADC Therapeutics stopped a Phase 1 study designed to characterize how liver impairment affects dosing of its approved lymphoma drug, closing it after enrolling a fraction of its target.
The company points to regulatory interactions and the difficulty of finding eligible patients with the specific degree of hepatic impairment the study required, not a safety problem.
The closure applies to a pharmacokinetic sub-study population and does not bear on the drug's approved use or its ongoing Phase 3 combination program in the same disease.
The closure adds to a run of early terminations across this sponsor's lifecycle studies for the same drug, a pattern worth tracking against its active later-stage programs.

The closure

ADC Therapeutics S.A. terminated NCT05660395, known as LOTIS-10, a Phase 1 open-label study testing the pharmacokinetics and safety of loncastuximab tesirine, sold as Zynlonta, in patients with relapsed or refractory diffuse large B-cell lymphoma or high-grade B-cell lymphoma who also had hepatic impairment. The trial's primary endpoint measured the number of participants with moderate or severe hepatic impairment who experienced a dose-limiting toxicity within the first 21-day treatment cycle. The company said the decision to close the study followed interactions with regulatory authorities and the challenges of enrolling this specific patient population, and stated that no safety information contributed to the decision. NCT05660395+1

Probability of Success

Endpoint Met10%

Completes48%

Clinical Significance18%

Regulatory42%

The enrollment gap

The study opened across sites in Brazil, South Korea, Taiwan, and the United States starting July 2023 with a target of 56 patients split across three hepatic-function arms: normal function, moderate impairment, and severe impairment. It closed having enrolled 5 patients, a shortfall against its own target that reflects the difficulty of finding lymphoma patients who also meet the trial's bilirubin and liver-function thresholds. The registry classifies the study as non-registrational, meaning it was designed to generate dosing information rather than to support an approval on its own. NCT05660395

What it does not touch

Zynlonta already carries FDA approval for relapsed or refractory large B-cell lymphoma after two or more prior lines of therapy, with the approval unaffected by this pharmacokinetic sub-study's closure. ADC Therapeutics also reported topline results from LOTIS-5, a Phase 3 trial combining Zynlonta with rituximab against immunochemotherapy in the same disease, which met its progression-free survival endpoint with a hazard ratio of 0.73 and a p-value of 0.008, alongside increases in serious adverse events and treatment withdrawals in the combination arm. That trial, not the hepatic-impairment study, is the one that carries the drug's near-term competitive stakes. NCT05660395

Sponsor track record

ADC Therapeutics has terminated Zynlonta studies before: a Phase 1/2 combination trial with ibrutinib closed in November 2022, and a Phase 1 combination study with R-CHOP was withdrawn in March 2024 before enrolling any patients. Across its broader pipeline, the sponsor has completed 5 of 15 trials with a documented outcome, while 10 were terminated, and its trials targeting B-cell surface antigens as a group show a 29% completion rate. None of those prior closures were tied to safety findings in the available record, and this pattern sits alongside two Zynlonta studies still active, including the Phase 3 LOTIS-5 program and an ongoing Phase 2 trial pairing Zynlonta with rituximab and DA-EPOCH-R. NCT05660395

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.