Zynlonta safety concerns rise as LOTIS-5 shows higher deaths

ADC Therapeutics’ LOTIS-5 phase 3 trial in relapsed/refractory DLBCL shows Zynlonta plus Rituxan improving progression-free survival (6.1 vs 4.7 months) and complete response rate (39.5% vs 26.7%), but with more deaths (27/440, 13.2% vs 9/440, 4.6%) and higher serious adverse events, driven largely by older patients and potentially influenced by longer monitoring in the treatment arm. There was no detrimental effect on overall survival. The safety signal spurred a roughly 52% drop in the company’s stock; ADC says it will meet with the FDA in August and plans to submit for full approval in Q4, with Zynlonta remaining the company’s sole marketed product.