ADC pauses Zynlonta lymphoma trial after deaths

clinical trial stopped
John Matychuk

Shares in ADC Therapeutics fell sharply after the company said it had suspended a trial of Zynlonta in previously untreated diffuse large B-cell lymphoma (DLBCL) patients following seven patient deaths.

The phase 2 LOTIS-9 study is investigating the combination of CD19 targeted antibody-drug conjugate Zynlonta (loncastuximab tesirine) with anti-CD20 antibody rituximab in an old and frail DLBCL patient population that currently has very few treatment options.

The deaths were mainly a result of respiratory problems, said the Swiss company, which already has conditional approvals in the US and EU for Zynlonta as a treatment for relapsed or refractory DLBCL after two or more lines of systemic therapy.

The voluntary action came after a review of the first 40 patients enrolled into the trial, which started dosing patients around a year ago. Along with seven deaths, there were five other cases of severe or life-threatening respiratory adverse events, according to a company statement, which suggested that 11 of the 12 cases were deemed by investigators as unlikely to be related to the drug treatment.

Despite that, shares in ADC Therapeutics fell 22% after the news, before recovering slightly in after-hours trading. Meanwhile, shares in Sobi, which licensed rights to Zynlonta in Europe last year, were also down slightly.

The company pointed out that LOTIS-9 enrolled a very old and frail patient population with an average age of almost 83, with all the deaths seen in patients with underlying conditions, including respiratory and cardiovascular diseases.

“Given the aggregate of the respiratory-related events seen in the trial, we implemented a voluntary pause of enrolment to allow for a thorough investigation of the data set,” said chief executive Ameet Malik.

“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,” he added. No additional data from the trial is expected before the end of the year.

LOTIS-9 is one of three pivotal trials that ADC Therapeutics is banking on to accelerate sales of Zynlonta, which brought in revenues of $19 million in the first quarter of this year.

The biotech was quick to point out that the deaths in LOTIS-9 were in patients that would have been excluded from its ongoing LOTIS-5 study of Zynlonta plus rituximab as a second-line therapy for DLBCL, which is due to generate results in the next 18 months.

Also on the go is LOTIS-7, a phase 1b study in relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) looking at combinations of Zynlonta and several other drugs, including Roche’s Polivy (polatuzumab vedotin), Gazyva (obinutuzumab), Columvi (glofitamab), and Lunsumio (mosunetuzumab).

Photo by John Matychuk on Unsplash.