ICML 2025 | Results from the LOTIS-7 trial: loncastuximab tesirine plus glofitamab in patients with R/R NHL

LOTIS-7 is an international Phase 1b clinical trial that evaluated the combination of loncastuximab with glofitamab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. The study consists of part 1, or dose escalation, where patients receive loncastuximab at 90, 120, and 150 mg per kilo with indolent and aggressive B-cell non-Hodgkin lymphoma treated with two or more lines of therapy. The dose expansion included loncastuximab at 120 or 150 mg per kilo for the first two cycles in combination with glofitamab in patients with aggressive histologies such as de novo diffuse large B-cell lymphoma, high-grade B-cell lymphoma, transformed follicular lymphoma, and follicular lymphoma grade 3B treated with one or more lines of therapy. Patients received obinutuzumab on day one and loncastuximab on day two, and subsequently on day eight started glofitamab at step-up doses. Starting on cycle two, the patients received on the same day loncastuximab with glofitamab with a fixed duration of loncastuximab for up to eight cycles and a fixed duration of glofitamab of up to 12 cycles. Regarding the safety analysis, the most common AE was neutropenia, which was similar in rates to single-agent loncastuximab and glofitamab without an additive effect on this toxicity. Other common AEs grade 3 or higher were anemia, thrombocytopenia, and GGT elevation. Importantly, there were no grade 5 toxicities. The incidence of CRS was low, with a lower incidence in the 150 compared to 120 mg per kilo dose level, and there were only three patients with the majority of them having grade one CRS, and there were only three patients that developed ICANS, one patient grade one, two patients grade two, there were no grade three or higher ICANS. In the efficacy analysis, the overall response rate was 93% with a CR rate of 86.5%. Importantly, the median duration of response was not reached, and the patients treated with a 150 mg dose level achieved a quicker response at 42 days compared to 80 days in the patients treated at 120 mg per kilo dose level. Among the 26 patients that achieved a complete response, 25 remain in remission at the time of the current follow-up. Two patients achieved a partial response that also maintained remission. Importantly, 12 patients that initially achieved a PR or a stable disease response subsequently improved to CR. Based on the shorter time to achieve a complete response and lower incidence of CRS, the trial now selected loncastuximab at 150 mg per kilo for the initial two doses and subsequently decreased to 75 mg per kilo for up to eight cycles, in combination with glofitamab for further expansion of the study cohort.

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