At the November 17, 2025, data cutoff, and with a minimum of 6 months of follow-up, 49 patients were evaluable for efficacy. The investigator-assessed best overall response rate (ORR) was 89.8% (n = 44), according to Lugano criteria. The complete response (CR) rate was 77.6% (n = 38), and 33 of these patients maintained their CR at data cutoff. The remaining 5 patients experienced progressive disease (n = 2), grade 5 adverse effects (AEs; n = 2), or were censored (n = 1).
“We’re excited that these data continue to demonstrate a manageable safety profile and strong efficacy including deep and durable responses in 2L+ [patients with] r/r DLBCL treated with [loncastuximab tesirine] plus glofitamab,” Mohamed Zaki, MD, PhD, chief medical officer of ADC Therapeutics, stated in a news release. “We are well on the way to completing enrollment of approximately 100 patients at the selected dose and plan to share full results at a medical congress and through a publication by the end of next year.”
What was the LOTIS-7 trial designed to evaluate?
LOTIS-7 is a global, multicenter, multi-arm, phase 1b study evaluating loncastuximab tesirine plus polatuzumab vedotin-piiq (Polivy), loncastuximab tesirine plus glofitamab, and loncastuximab tesirine plus mosunetuzumab (Lunsumio) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma in dose escalation and dose expansion cohorts.2
In part 1 of the study patients will be subject to a 3+3 dose escalation of loncastuximab tesirine doses starting at 90 µg/kg and then escalating to 120 µg/kg and 150 µg/kg as third or later-line treatment. Part 2 will include dose expansion in the loncastuximab tesirine and glofitamab arm for patients with large B-cell lymphoma in need of second or later-line treatment at dose levels determined from part 1.
The primary end points of the study are safety and tolerability. Key secondary end points include ORR, duration of response, CR rate, progression-free survival, relapse-free survival, and overall survival in addition to pharmacokinetics and immunogenicity.
What was the efficacy of the regimen according to disease status?
The ORR was 100% in the relapsed population (n = 24) and the CR rate was 91.7%.1 One patient with stable disease (SD) or partial response (PR) later achieved CR. Among patients with primary refractory disease (n = 25), the ORR was 80% and the CR rate was 64%. A total of 13 patients who initially experienced SD or PR later experienced CR.
Moreover, 75% (n = 6) of patients who had previously been treated with CAR T-cell therapy (n = 8) achieved CR.
How was the safety profile of the combination described?
Grade 3 or higher treatment-emergent AEs that occurred in more than 5% of patients included neutropenia (32.7%), increased gamma-glutamyl transferase levels (16.3%), anemia (10.2%), decreased white blood cell count (8.2%), generalized edema (8.2%), increased alanine aminotransferase levels (8.2%), increased aspartate aminotransferase levels (6.1%), and thrombocytopenia (6.1%).
Of the 2 grade AEs that occurred, 1 was deemed treatment-related by the investigator.
Any-grade cytokine release syndrome (CRS) occurred in 36.7% of patients, and all but 1 were low-grade events. Fewer patients experienced CRS at the selected dose of 150 µg/kg (25%) vs the 120-µg/kg dose (52.4%). Immune effector cell–associated neurotoxicity syndrome occurred in 4.1% of patients across dose levels, and all events were grade 1 or 2.
What are the next steps for the LOTIS-7 trial?
The LOTIS-7 trial remains open to accrual. Investigators expect to complete enrollment of approximately 100 patients at the selected 150-µg/kg dose during the first half of 2026. ADC Therapeutics also intends to share the full findings at an upcoming medical meeting and submit the data for publication by the end of 2026.
“We believe these updated data further strengthen the evidence supporting the differentiated profile of the combination of [loncastuximab tesirine] and glofitamab, which has the potential to be the best-in-class bispecific antibody-based combination in 2L+ DLBCL,” Ameet Mallik, chief executive officer of ADC Therapeutics, stated in a news release. “Taken together with the LOTIS-5 trial, for which top-line results are anticipated in the first half of 2026, we believe [loncastuximab tesirine]–based combinations offer complementary approaches with the potential to improve outcomes for 2L+ [patients with] DLBCL.”
References
- ADC Therapeutics announces updated data from LOTIS-7 phase 1b clinical trial of Zynlonta in combination with bispecific antibody supporting potential best-in-class regimen in patients with relapsed/refractory diffuse large B-cell lymphoma. News release. ADC Therapeutics. December 3, 2025. Accessed December 4, 2025. https://ir.adctherapeutics.com/2025-12-03-ADC-Therapeutics-Announces-Updated-Data-from-LOTIS-7-Phase-1b-Clinical-Trial-of-ZYNLONTA-R-in-Combination-with-Bispecific-Antibody-Supporting-Potential-Best-in-Class-Regimen-in-Patients-with-Relapsed-Refractory-Diffuse-Large-B-cell-Lymphoma
- A study to evaluate the safety and anti-cancer activity of loncastuximab tesirine in combination with other anti-cancer agents in participants with relapsed or refractory B-cell non-Hodgkin lymphoma (LOTIS-7). ClinicalTrials.gov. Updated November 13, 2025. Accessed December 4, 2025. https://clinicaltrials.gov/study/NCT04970901
