Overview of Clinical Trial Update

ADC Therapeutics announced updated results from its LOTIS-7 Phase 1b open-label clinical trial evaluating the antibody-drug conjugate (ADC) ZYNLONTA® in combination with the bispecific antibody glofitamab (COLUMVI®) for patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). The presentation was made at the European Hematology Association (EHA) 2025 Congress in Milan, Italy.

Efficacy Highlights

Among 30 patients evaluable for efficacy, the overall response rate (ORR) was 93.3%, with a complete response (CR) rate of 86.7%. Of the 26 patients achieving CR, 25 remained in CR at data cut-off, suggesting durable remissions. The patient cohort included individuals previously treated with various agents, including CAR-T therapies, underscoring the regimen’s potential in heavily pre-treated populations.

Safety and Tolerability

The combination demonstrated a manageable safety profile consistent with previous studies. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) incidences were low, indicating the regimen’s tolerability even at higher ZYNLONTA dosing levels (120 µg/kg and 150 µg/kg).

Trial Expansion and Future Plans

Enrollment for LOTIS-7 is expanding to 100 patients at the 150 µg/kg dose level. Further data are anticipated to refine dosing strategies and confirm long-term outcomes. ADC Therapeutics is committed to advancing this novel combination as a transformative option for r/r DLBCL patients.

Mechanism of Action

ZYNLONTA® specifically targets CD19-expressing B-cells delivering a potent cytotoxic payload, while glofitamab engages CD3 on T-cells and CD20 on B-cells facilitating robust T-cell-mediated killing of lymphoma cells. This dual targeting may enhance efficacy compared to single-agent therapies.

Industry Significance

This combination exemplifies next-generation immuno-oncology approaches integrating ADC delivery with bispecific T-cell engagement to overcome resistance mechanisms and deepen response durability. It also heralds a new therapeutic option for patients with poor prognoses and limited alternatives.