Phase Ib Initial Data: Loncastuximab Tesirine-lpyl plus Glofitamab Effective, Safe in DLBCL

Initial data reported from the LOTIS-7 phase Ib clinical trial support loncastuximab tesirine-lpyl plus glofitamab combination as an effective and safe treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

These results were announced in a press release from ADC Therapeutics, a Switzerland-based antibody drug conjugate (ADC) developer, which markets loncastuximab tesirine-lpyl as Zynlonta.

In the ongoing LOTIS-7 international, open-label study, 18 patients with relapsed or refractory DLBCL received loncastuximab tesirine-lpyl, a CD-19–directed ADC, in combination with glofitamab, a bispecific antibody. Two dosages of loncastuximab tesirine-lpyl were tested, 120 µg/kg and 150 µg/kg, with nine patients receiving each.

Regarding efficacy results in the total cohort, the best overall response rate (ORR) was 94%; 72% of patients achieved a complete response (CR), and 22%, a partial response. Among patients in the 150 µg/kg dose group, the best ORR attained was 100%, and 78% of patients achieved a CR.

Safety with the combination was evaluated in 29 patients with relapsed or refractory B-cell non-Hodgkin lymphomas. There were no dose-limiting toxicities. The most prevalent grade 3 or higher treatment-emergent adverse events (TEAEs) were neutropenia in 24% of patients, lymphopenia in 7%, and hypokalemia in 7%; there were no grade 5 TEAEs. There were also no cases of grade 3 or higher cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS). Grade 1 or 2 CRS affected 34.5% of patients but resolved with standard treatment, and two patients had grade 2 ICANS whose symptoms completely resolved.

“We believe these data support our hypothesis that combining these two potent, approved, single-agent-drugs with complementary mechanisms of action will yield additive or synergistic efficacy, and a manageable safety profile given no overlapping non-hematologic toxicities, enabling administration across care settings,” wrote Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics.

Loncastuximab tesirine-lpyl has received accelerated approval from the FDA and conditional approval from the European Commission to treat relapsed or refractory DLBCL after at least two lines of systemic therapy. Clinical research is also underway on use of this ADC in earlier lines of therapy and in other combinations.

Source: ADC Therapeutics Press Release, December 2024, PR Newswire