Severe respiratory problems killed seven patients and affected five others, though the company said that most of these were likely unrelated to the drug.
Pictured: Photograph of an empty bed in a hospital room/iStock, robypangy
ADC Therapeutics announced on Tuesday that it has ceased enrollment of new patients in a Phase II of Zynlonta along with rituximab for patients with previously untreated diffuse large B cell lymphoma (DLBCL), a type of blood cancer. The reason: seven patient deaths due to extreme respiratory events.
The LOTIS-9 trial has thus far enrolled 40 participants who received the combination of Zynlonta and rituximab. Almost one-third of these participants developed respiratory issues following the treatment. Among the 12 participants who experienced respiratory-related events, there were seven Grade 5 that led to the patients’ deaths and five Grade 3 or 4.
The cancer patients who passed away were 80 years of age or older and were suffering from existing comorbid conditions such as chronic obstructive pulmonary disease idiopathic pulmonary fibrosis or recent COVID-19 infection.
ADC assessed that 11 of 12 of the events, including six of the deaths, were “unlikely or unrelated to study drug.” The company said that it put a voluntary pause to investigate the data and determine the next steps.
“Our top priority is the safety of every patient who participates in our clinical trials,” Ameet Mallik, ADC Therapeutics CEO, said in the release.
For now, ADC has informed regulatory authorities, including the FDA and EMA, and doesn’t expect to report further data by the end of the year.
TD Cowen analyst Boris Peaker suggested that the safety concerns could be due to the combinations of Zynlonta along with rituximab. “A lower dose of Zynlonta may be worth exploring given the high efficacy,” Peaker wrote in a note to investors, according to Endpoints News.
Zynlonta received an accelerated approval in 2021 from FDA for the treatment of adults with DLBCL, after two prior lines of treatments. It was the first single-agent CD19-targeted antibody drug to be approved for DLBCL based on Phase II trial that showed it has positive effect on about 48.3% patients.
The LOTIS-9 clinical trial is a part of ADC’s attempt to grow Zynlonta’s label as a first option for patients with DLBCL. ADC is also running a separate clinical trial of Zynlonta as a second option for DLBCL patients. Peaker noted that it’s likely that the LOTIS-9 trial will need to be modified to a lower dose or exclude certain patients.
Last year, ADC Therapeutics entered into a partnership with Sobi in a deal worth $435 million. This partnership allows Sobi to manufacture and market Zynlonta outside of the U.S., except for certain countries in Asia. Additionally, ADC Therapeutics has collaborated with Avid Bioservices to increase the production of Zynlonta at a facility in Tustin, California, to meet the demand for the drug.
ADC Therapeutics shares sank 21% after the company released today’s news of the adverse events in the LOTIS-9 trial.
Maaisha Osman is an independent science writer based in D.C. Reach her at maaisha.07@gmail.com or on Twitter @MaaishaO.
