ADC Therapeutics discontinued clinical trials after the patient’s death

ADC Therapeutics SA has announced a voluntary pause in new patient enrollment in its phase 2 LOTIS-9 clinical trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) and rituximab (Lonca-R) in patients who are otherwise healthy or debilitated with diffuse large B who were not previously treated cell lymphoma (DLBCL).

The action was taken by ADC Therapeutics following a recent review of aggregated data from 40 patients enrolled in the trial and consultation with the Data Monitoring Committee (DMC), which signaled the possibility of an excessive breathing-related event. These respiratory-related treatment-related adverse events (TEAE) included seven Grade 5 fatalities and five Grade 3 or Grade 4 respiratory-related TEAEs.

Based on investigator judgment, 11 of 12 events (including six of seven Grade 5 fatal events) were rated individually as unlikely or unrelated to the drug of study. Four of the five Grade 3 or Grade 4 events have resolved and the patient has completed treatment according to the protocol. The cause of this incident is still under further investigation.

All patients with a fatal event had one or more significant active respiratory and/or cardiac co-morbidities including severe chronic obstructive pulmonary disease (COPD), pulmonary edema, chronic bronchiectasis, idiopathic pulmonary fibrosis and recent COVID-19 infection and all greater than or equal to 80 years.

The mean age was 82.7 years and the mean number of days from last dose to death was 51 days, with a range of 19 to 86 days. It is important to note that all 12 patients with TEAE Grades 3–5 in the LOTIS-9 study will be excluded from the LOTIS-5 trial.

ADC Therapeutics evaluates the data

ADC Therapeutics’ decision to pause enrollment allows time to evaluate the data surrounding TEAE and determine next steps. The company has notified all study investigators and regulatory authorities including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) of the company’s decision to terminate the registration. The company doesn’t expect to report additional data from the trial by the end of the year.

“Our top priority is the safety of every patient participating in our clinical trials,” said Ameet Mallik, CEO of ADC Therapeutics.

“Given the aggregate of respiratory-related events seen in the trials, we implemented a voluntary enrollment gap to allow thorough investigation of the data set. This trial includes a very difficult-to-treat patient population with limited treatment options, and we will provide updates on next steps when they become available.”