ADC Therapeutics, a biotechnology company specializing in the development of antibody-drug conjugates (ADCs) for the treatment of hematological malignancies and solid tumors, has recently provided updates on its ongoing LOTIS-7 clinical trial. This trial aims to evaluate the combination of ZYNLONTA (loncastuximab tesirine-lpyl) with either glofitamab or mosunetuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). The trial has now completed the dose escalation in its Phase 1b stage, demonstrating promising results with no dose-limiting toxicities and early signs of anti-tumor activity.
Non-Hodgkin lymphoma is a cancer that originates in the lymphatic system, which is a part of the body’s immune system. B-cell NHL is a common subtype of this cancer, characterized by abnormal growth of B-lymphocytes, a type of white blood cell. Despite recent advancements in treatment options, a significant number of patients experience relapse or refractory disease, highlighting the need for innovative therapeutic approaches.
ZYNLONTA, developed by ADC Therapeutics, is an ADC that specifically targets CD19, a protein present on the surface of B-cells. It combines a monoclonal antibody with a potent cytotoxic agent, resulting in targeted killing of CD19-expressing cells. Glofitamab and mosunetuzumab are bispecific antibodies that engage both CD20, found on B-cells, and CD3, present on T-cells. These bispecific antibodies redirect T-cell activity towards eliminating the cancerous B-cells.
The LOTIS-7 trial investigates the safety and efficacy of combining ZYNLONTA with either glofitamab or mosunetuzumab in patients who have relapsed or are refractory to previous treatment options. The Phase 1b dose escalation stage has been successfully completed, with no dose-limiting toxicities reported. Additionally, the trial observed no or low-grade cytokine release syndrome (CRS) and no immune effector cell-associated neurotoxicity syndrome (ICANS) across all patients. CRS and ICANS are potential side effects associated with immunotherapies that activate the immune system.
Furthermore, early signs of anti-tumor activity have been observed in patients treated with ZYNLONTA in combination with glofitamab or mosunetuzumab, suggesting the potential for significant clinical benefits. Anti-tumor activity refers to the ability of the treatment to suppress or eradicate tumor growth.
These promising results highlight the potential of combining ADCs with bispecific antibodies to effectively target and eliminate cancer cells in patients with relapsed or refractory B-cell NHL. By utilizing different mechanisms of action, these therapies have the potential to overcome resistance developed by cancer cells in response to previous treatments.
The completion of the dose escalation stage without any dose-limiting toxicities is a significant milestone for the trial. This indicates that the combination therapies are well-tolerated by patients and may have a favorable safety profile. The absence or low-grade nature of CRS and ICANS also suggests that the immune system is not overly activated, further supporting the rationale for this treatment approach.
The observed early signs of anti-tumor activity are encouraging, as they demonstrate that the combination therapies have the potential to effectively target and eliminate cancer cells. While further research is required to establish the full extent of the clinical benefits and long-term outcomes, these preliminary results provide a promising foundation for future investigations.
In conclusion, ADC Therapeutics’ latest updates on the LOTIS-7 clinical trial evaluating ZYNLONTA in combination with glofitamab or mosunetuzumab in patients with relapsed or refractory B-cell NHL show significant progress. The completion of the Phase 1b dose escalation stage without dose-limiting toxicities, low-grade CRS and ICANS, along with early signs of anti-tumor activity, is a testament to the potential of this treatment approach. These results pave the way for further development of ADCs and bispecific antibodies in the treatment of hematological malignancies, ultimately offering hope to patients in need of innovative therapeutic options.
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