ADC Therapeutics Reports Positive Early Results from LOTIS-7 Trial on ZYNLONTA® with Bispecific Antibody in Relapsed/Refractory DLBCL

In a recent announcement, ADC Therapeutics SA, a recognized leader in antibody drug conjugates, disclosed promising initial results from their ongoing LOTIS-7 Phase 1b clinical trial. This trial is investigating the combination of ZYNLONTA and the bispecific antibody glofitamab for patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). The trial aims to evaluate the safety and efficacy of this drug combination in addressing the needs of patients who have limited treatment options.

According to Dr. Mohamed Zaki, Chief Medical Officer at ADC Therapeutics, the initial findings are encouraging. The combination of ZYNLONTA and glofitamab has been observed to provide a clinically meaningful benefit in the trial, achieving a remarkable best overall response rate of 94% and a complete response rate of 72%. These results suggest that the two drugs, which have different but complementary mechanisms of action, could work synergistically to enhance therapeutic outcomes.

The LOTIS-7 trial is structured in two parts: Part 1 focuses on dose escalation, while Part 2 emphasizes dose expansion. As of November 20, 2024, 29 patients with B-cell non-Hodgkin lymphoma had been treated and evaluated for safety in both parts of the trial. In terms of efficacy, the analysis included 18 evaluable patients with relapsed or refractory DLBCL who received ZYNLONTA at dose levels of either 120 µg/kg or 150 µg/kg in combination with glofitamab.

Safety assessments indicated that the combination therapy was generally well tolerated across all dose levels, with no dose-limiting toxicities reported. Importantly, there were no instances of high-grade cytokine release syndrome or high-grade immune effector cell-associated neurotoxicity syndrome, conditions that can be concerning in similar immunotherapies.

Ameet Mallik, the CEO of ADC Therapeutics, expressed optimism about the potential of this drug combination to become a leading treatment option in this competitive market. The company is now focused on completing the enrollment for the dose expansion phase by the first half of 2025. Moreover, ADC Therapeutics plans to engage with regulatory bodies to discuss future steps, especially as more data become available from additional patients with longer follow-up periods.

The LOTIS-7 trial encompasses a global, multi-center, and multi-arm study, investigating not only ZYNLONTA and glofitamab but also other combinations such as ZYNLONTA with polatuzumab vedotin and mosunetuzumab, which are T-cell-engaging bispecific monoclonal antibodies. Each dosing arm aims to identify the best approaches for treating relapsed or refractory B-cell non-Hodgkin lymphoma.

ADC Therapeutics has established itself as a pioneer in developing antibody drug conjugates, with its proprietary ADC technology showing promise in treating hematologic malignancies and solid tumors. ZYNLONTA, one of their flagship products, received expedited approval from both the FDA and the European Commission for treating relapsed or refractory diffuse large B-cell lymphoma after multiple lines of systemic therapy. The drug is also being explored in combination with other agents in various treatment lines.

Based in Lausanne, Switzerland, ADC Therapeutics continues to expand its operations and is committed to transforming treatment paradigms for challenging cancers through innovative therapeutic approaches.