ADC Discontinues Zynlonta Trial in DLBCL After Seven Deaths

Pictured: Doctor checking a patient's neck/iStock, stefanamer

Pictured: Doctor checking a patient's neck/iStock, stefanamer

ADC Therapeutics is discontinuing the Phase II LOTIS-9 trial testing Zynlonta (loncastuximab tesirine-lpyl) in combination with Genentech and Biogen’s Rituxan (rituximab) for patients with previously untreated diffuse large B-cell lymphoma, the company announced Thursday afternoon.

The decision to discontinue comes after the Swiss biotech decided last week to voluntarily halt enrollment in LOTIS-9 after seven patients died of extreme respiratory events. While six of the fatalities were deemed “unlikely or unrelated to the study drug,” the company nevertheless elected to suspend the entry of patients into the study.

In connection with the deaths, the FDA has also placed a partial clinical hold on enrollment into LOTIS-9, according to ADC’s Thursday press release. However, the company can continue dosing diffuse large B-cell lymphoma (DLBCL) patients who were seeing clinical benefit from the experimental treatment regimen, as long as these patients have given their consent again.

Once the treatment of these reconsenting patients have concluded, ADC will wrap up the trial and has no plans of studying the investigational regimen in this indication and specific patient population in the future.

“Given the challenges of defining the addressable segment of the difficult-to-treat unfit or frail DLBCL patient population, including many patients with significant active underlying co-morbidities, the benefit-risk profile does not support continuation of the LOTIS-9 trial,” the company said on Thursday.

LOTIS-9 was an open-label study that enrolled 80 DLBCL patients who were deemed difficult-to-treat, unfit or frail. The study tested an investigational regimen that combined the anti-CD20 action of Rituximab with Zynlonta, which targets the CD19 protein, often found on the surface of B cells.

Zynlonta is an antibody-drug conjugate that works by binding to the transmembrane CD19 protein, in turn inducing the cell to internalize the drug. Once inside the cell, Zynlonta delivers its cytotoxic payload SG3199, which has the effect of tangling the DNA and eventually leading to cell death.

ADC scored a regulatory win for Zynlonta in April 2021, when the FDA authorized its use as the first CD19-targeted antibody-drug conjugate for relapsed or refractory diffuse large B-cell lymphoma. Sales for Zynlonta have been disappointing though, with the medicine bringing in only $19 million in the first quarter of 2023. This represents a 15% increase from the same period a year prior, but also a slight decline from fourth quarter 2022 sales.

To cut costs, ADC implemented an updated corporate strategy in May 2023, which involved a 17% reduction in headcount.

Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at or

Back to news