ADC Therapeutics has slammed the brakes on enrollment in a phase 2 combination trial for Zynlonta as it investigates seven patient deaths and five other severe respiratory events among patients who received the drug.
For the study in unfit or frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL), investigators had enrolled 40 participants. After receiving the ADC drug, 12 of them experienced respiratory-related, treatment-emergent adverse events, ADC said in a Tuesday release.
The investigators concluded that 11 of the events, including six of the deaths, were "unrelated" to the Zynlonta treatment or unlikely to be related to the drug, ADC said.
All of the patients who died suffered from at least one "significant" comorbidity, including obstructive pulmonary disease, pulmonary edema, chronic bronchiectasis, idiopathic pulmonary fibrosis or recent COVID-19 infection. All of the patients who passed away were at least 80 years of age, according to the company.
ADC said it put a "voluntary pause" on the trial to gain more time to "evaluate data … and determine next steps." The study was testing ADC's medicine in combination with Roche's Rituxan.
“Our top priority is the safety of every patient who participates in our clinical trials,” CEO Ameet Mallik said in the company’s statement. “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.”
ADC has notified the FDA and the European Medicines Agency (EMA) and doesn’t expect to report any additional trial data by the end of the year.
Zynlonta won approval in 2021 under the FDA's accelerated pathway as a solo treatment for adults with relapsed or refractory DLBCL after two prior lines of therapy. It was the first single-agent CD19-targeted antibody-drug conjugate to be cleared for the disease after posting an overall response rate of 48.3% in a phase 2 trial.
Last summer, ADC teamed up with Sobi in a $435 million deal allowing the Swedish company to make and market the drug outside of the U.S., save for greater China, Singapore and Japan. And the company previously tapped Avid Bioservices to ramp up commercial manufacturing for the drug at its Tustin, California, facility.
Before the Sobi deal, ADC in May shook up its leadership by appointing Novartis vet Mallik as chief executive, replacing co-founder Chris Martin. The following month, Mallik brought in former Novartis exec David Gilman to lead business and strategy.