ADC Therapeutics Discontinues Zynlonta Trial After 7 Deaths Led to An FDA Partial Hold
ADC Therapeutics, a biotechnology company, has decided to discontinue its Zynlonta trial following a partial clinical hold imposed by the FDA. The trial was evaluating the drug, in combination with Roche’s Rituxan, for unfit or frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL).
The decision to halt the study came after the company reviewed seven deaths and five other respiratory events in patients who received the drug. Out of the 12 respiratory-related adverse events that contributed to the decision, 11 were determined to be “unrelated” or unlikely to be associated with Zynlonta treatment. However, all seven patients who died were at least 80 years old and had at least one significant comorbidity.
ADC cited difficulties in defining the target patient population for the difficult-to-treat population as one of the reasons for discontinuing the trial. The benefit-risk profile was deemed unsupportive of continuing the study.
The FDA placed a partial hold on enrolling new patients in the trial, but patients who were already receiving the drug and showing clinical benefits could continue after reconsenting.
Zynlonta had received FDA approval in 2021 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 approved, with an overall response rate of 48.3% in a phase 2 trial.
In addition to scrapping the Zynlonta trial, ADC also disclosed plans to lay off 17% of its workforce, including contractors, as part of a new corporate and capital allocation strategy. The company decided to halt investment in two preclinical cancer programs in favor of focusing on the most advanced, lower-risk value-generating programs. ADC had experienced leadership changes, with Ameet Mallik becoming the CEO, and David Gilman, a former Novartis executive, being brought in to lead business and strategy.
