The phase 2 LOTIS-9 clinical trial (NCT05144009) investigating the combined use of loncastuximab tesirine-lpyl (Zynlonta®) and rituximab, together called Lonca-R, in unfit or frail patients with diffuse large B-cell lymphoma (DLBCL) has paused new patient enrollment, according to a press release from ADC Therapeutics, the manufacturer of loncastuximab tesirine-lpyl.
The pause was initiated after a review of aggregate data on the enrolled patients and consultation with the Data Monitoring Committee revealed a potentially large number of respiratory-related events. Respiratory-related treatment-emergent adverse events (TEAEs) included 5 grade 3 or 4 TEAEs and 7 grade 5 fatal events. ADC Therapeutics will use the pause to investigate the data around the TEAEs to determine the next steps.
“Our top priority is the safety of every patient who participates in our clinical trials,” said Ameet Mallik, chief executive officer of ADC Therapeutics. “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.”
Of the 12 TEAEs, 11 were assessed as unlikely or unrelated to the study drug, including 6 of the 7 fatal events, by the study investigator. Resolution of symptoms occurred in 4 out of the 5 TEAEs of grade 3 or 4 and those patients completed the treatment protocol.
All of the patients who experienced fatal events had 1 or more significant underlying respiratory and/or cardiac comorbidities and were aged 80 or more years. Comorbidities included pulmonary edema, chronic bronchiectasis, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and recent COVID-19 infection.
Read more about loncastuximab tesirine-lpyl for DLBCL.
The LOTIS-9 trial has currently enrolled 40 patients in the study. Of the 30 patients who were enrolled as of May 10, 2023, 13 were enrolled in cohort A which included those who were unfit and 17 were enrolled in cohort B including frail patients or those with cardiac comorbidities.
Of the 17 patients in both cohorts who had completed a baseline and at least 1 post-baseline assessment by the data cutoff date, 10 had achieved a complete response, 6 had a partial response, and 1 had stable disease, as determined by an investigator.
Loncastuximab tesirine-lpyl is approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma, including DLBCL arising from low-grade lymphoma, high-grade B-cell lymphoma, and DLBCL not otherwise specified, after 2 or more lines of systemic therapy.
ADC Therapeutics announces voluntary pause of enrollment in the phase 2 LOTIS-9 clinical trial of Zynlonta® (loncastuximab tesirine-lpyl) and rituximab in unfit or frail previously untreated DLBCL patients. News release. ADC Therapeutics; July 11, 2023.