ZYNLONTA Plus Glofitamab Achieves 89.8% Response Rate in Relapsed/Refractory DLBCL Trial
Key Insights
ADC Therapeutics reported updated LOTIS-7 Phase 1b trial data showing ZYNLONTA combined with glofitamab achieved an 89.8% overall response rate and 77.6% complete response rate in 49 patients with relapsed or refractory diffuse large B-cell lymphoma (search).
The combination demonstrated strong efficacy across both relapsed and primary refractory patient populations, with 100% response rate in relapsed patients and 80% in primary refractory patients.
The treatment was generally well-tolerated with manageable safety profile, including 36.7% cytokine release syndrome across all dose levels and only 4.1% immune effector cell-associated neurotoxicity syndrome.
ADC Therapeutics announced promising updated results from its LOTIS-7 Phase 1b clinical trial, demonstrating that the combination of ZYNLONTA (loncastuximab tesirine-lpyl) with the bispecific antibody glofitamab (COLUMVI) achieved an 89.8% overall response rate in patients with relapsed or refractory diffuse large B-cell lymphoma (search) (r/r DLBCL).
Strong Efficacy Across Patient Populations
The updated data, based on 49 efficacy-evaluable patients with a minimum of 6 months follow-up from treatment initiation, showed a complete response (CR) rate of 77.6% (38/49 patients). Notably, 33 of the 38 patients achieving complete response remained in CR as of the November 17, 2025 data cutoff.
"We're excited that these data continue to demonstrate a manageable safety profile and strong efficacy including deep and durable responses in 2L+ r/r DLBCL patients treated with ZYNLONTA plus glofitamab," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics.
The combination showed particularly strong results across different patient subgroups. In the 24 relapsed patients, the overall response rate was 100% with a complete response rate of 91.7%. Among the 25 primary refractory patients, the overall response rate was 80% with a complete response rate of 64%.
Response Conversion and CAR-T Experience
The trial demonstrated the potential for response deepening over time, with 14 patients converting from stable disease or partial response to complete response. Of particular interest, among the 8 patients previously treated with CAR-T therapy, 6 achieved a complete response.
Manageable Safety Profile
The combination was generally well-tolerated with a manageable safety profile. Grade 3 or higher treatment emergent adverse events observed in more than 5% of patients included neutropenia (32.7%), GGT increased (16.3%), anemia (10.2%), WBC decreased (8.2%), generalized oedema (8.2%), ALT increased (8.2%), AST increased (6.1%), and thrombocytopenia (6.1%).
Cytokine release syndrome (CRS) of all grades across dose levels was 36.7%, with CRS all grades occurring in 25.0% of patients at the selected 150 μg/kg dose and 52.4% at the 120 μg/kg dose. Importantly, all but one case was low grade. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 4.1% of patients across dose levels, with only Grade 1/2 severity.
Grade 5 adverse events occurred in 2 (4.1%) patients, with one considered treatment-related per the investigator assessment.
Trial Design and Future Plans
LOTIS-7 is a Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (search). The study includes dose escalation (Part 1) and dose expansion (Part 2) phases, with three dosing arms evaluating ZYNLONTA in combination with different agents including glofitamab.
Enrollment in the LOTIS-7 clinical trial is ongoing, with complete enrollment of approximately 100 patients at the selected 150 μg/kg dose expected during the first half of 2026. The company plans to share full data at a medical meeting and submit for publication by the end of 2026, along with assessing regulatory and compendia strategies.
"We believe these updated data further strengthen the evidence supporting the differentiated profile of the combination of ZYNLONTA and glofitamab, which has the potential to be the best-in-class bispecific antibody-based combination in 2L+ DLBCL," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics.
About ZYNLONTA
ZYNLONTA is a CD19 (search)-directed antibody drug conjugate that has received accelerated approval by the FDA and conditional approval from the European Commission for treating adult patients with relapsed or refractory large B-cell lymphoma (search) after two or more lines of systemic therapy. The drug utilizes a pyrrolobenzodiazepine payload that binds to DNA minor groove, ultimately resulting in cell cycle arrest and tumor cell death.