ADC Therapeutics SA has announced a voluntary pause in the enrollment of new patients in the phase 2 LOTIS-9 clinical trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) and rituximab (Lonca-R) in unfit or frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL).
The action was taken by ADC Therapeutics after a recent review of aggregate data of the 40 patients enrolled in the trial and consultation with the Data Monitoring Committee (DMC), which signaled potentially excessive respiratory-related events. These respiratory-related treatment-emergent adverse events (TEAEs) included seven Grade 5 fatal events and five Grade 3 or Grade 4 respiratory-related TEAEs.
As per investigator assessment, 11 of the 12 events (including six of the seven Grade 5 fatal events) were individually assessed as unlikely or unrelated to the study drug. Four out of the five Grade 3 or Grade 4 events have since resolved and the patients have completed treatment per protocol. The cause of these events remains under further investigation.
All patients with fatal events had one or more significant active underlying 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 were greater than or equal to 80 years of age.
The mean age was 82.7 years and the mean number of days from the last dose to death was 51 days, with a range of 19 to 86 days. It is important to note that all 12 of the patients with Grade 3-5 TEAEs in the LOTIS-9 study would have been excluded from the LOTIS-5 trial.
ADC Therapeutics evaluating data
ADC Therapeutics’ decision to pause enrollment enables time to evaluate data around the TEAEs and determine next steps. The company has notified all study investigators and regulatory authorities including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) of the company’s decision to pause enrollment. The company does not expect to report additional data from the trial by the end of the year.
“Our top priority is the safety of every patient who participates in our clinical trials,” said Ameet Mallik, chief executive officer of ADC Therapeutics.
“Given the aggregate of the respiratory-related events seen in the trial, we implemented a voluntary pause of enrollment to allow for a thorough investigation of the data set. This trial includes a very difficult-to-treat patient population with limited treatment options, and we will provide an update on next steps when available.”