Source – ADC Therapeutics
ADC Therapeutics has halted enrollment in a Phase II combination trial for Zynlonta following the investigation of seven patient deaths and five severe respiratory events among participants who received the drug.
On 11 July 2023, the trial aimed to evaluate Zynlonta in unfit or frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL) and had enrolled 40 participants. 12 patients experienced respiratory-related adverse events after receiving the ADC drug.
After careful evaluation, investigators concluded that 11 of the events, including six deaths, were not related or unlikely to be linked to the Zynlonta treatment, as stated by ADC. All patients who passed away had significant comorbidities such as obstructive pulmonary disease (COPD), pulmonary edema, chronic bronchiectasis, idiopathic pulmonary fibrosis, or recent COVID-19 infection. Additionally, all the deceased patients were at least 80 years old.
“Our top priority is the safety of every patient who participates in our clinical trials,” 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.”
– CEO Ameet Mallik
ADC has informed the FDA and the European Medicines Agency (EMA) about the situation and does not anticipate reporting any additional trial data by the end of the year.
Since the data cutoff of May 10, 2023, there has been an additional occurrence of the most severe adverse events (Grade 5 events), bringing the total to seven such events. Out of these seven patients, two died within 30 days after receiving the last doses of the study medication. The remaining five patients passed away more than 30 days following their last dose, with the time range varying from 41 to 86 days. Adverse events are classified using MedDRA version 24.1, and their severity is evaluated using CTCAE v5.0. Only adverse events that emerged during treatment are summarized, and each patient is included only once for each specific system organ class and preferred term.
Zynlonta received accelerated approval from the FDA in 2021 as a standalone treatment for adults with relapsed or refractory DLBCL after two prior lines of therapy. It became the first single-agent CD19-targeted antibody-drug conjugate to be cleared for the disease based on a Phase II trial that demonstrated an overall response rate of 48.3%.
Last year, ADC entered a collaboration with Sobi, allowing the Swedish company to manufacture and market Zynlonta outside of the US, with the exception of greater China, Singapore, and Japan. Furthermore, ADC had previously partnered with Avid Bioservices to enhance commercial manufacturing of the drug at its facility in Tustin, California.
