Clinical data from an ongoing phase I clinical trial evaluating ADCT-402 for the treatment of relapsed or refractory non-Hodgkin lymphoma was presented at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland. ADCT-402 is a novel antibody-drug conjugate composed of a humanized monoclonal antibody that binds to human CD19, conjugated to the pyrrolobenzodiazepine dimer toxin. CD19 is highly expressed in a wide range of B-cell hematologic tumors, including certain forms of lymphomas and leukemias, whereas its expression in healthy tissues is restricted.
In a presentation at the 14th ICML, interim results from the phase I, open-label, dose-escalating study of ADCT-402 evaluating tolerability, safety, pharmacokinetics, and efficacy in patients with relapsed or refractory non-Hodgkin lymphoma were reported. Data were presented from 62 evaluable patients with a median age of 67 years and a median of 3 previous therapies (range, 1–10).
The overall response rate with doses ≥ 120 µg/kg was 61% in the total patient population (42% complete response, 19% partial response). In patients with relapsing or refractory diffuse large B-cell lymphoma, the overall response rate was 57% (43% complete response, 14% partial response). The maximum tolerated dose has not yet been reached.
Among the patients enrolled at the time of the data cutoff for presentation, ADCT-402 has been reasonably well-tolerated, with the most common treatment emergent adverse events being fatigue, neutropenia, and thrombocytopenia, which have been treated symptomatically and, in some cases, with dose delays, reductions, and discontinuation.
Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said, “These clinical data provide additional support for the efficacy and tolerability of ADCT-402, as well as of our [antibody-drug conjugate] technology platform based on [pyrrolobenzodiazepine] warheads. In preclinical studies, the [pyrrolobenzodiazepine] dimer toxin has been shown to be a highly potent killer of cancer cells—even in hard-to-treat tumors. The presented results confirm the potential role of ADCT-402 in the treatment of relapsed and refractory non-Hodgkin lymphoma. We believe these findings reflect a strong path forward, and we are looking forward to getting further results later this year.”
“These early findings are very encouraging, as they demonstrate a clear clinical benefit and manageable toxicity for patients who [had standard treatment fail] or are intolerant to any established therapy,” said principal investigator Brad Kahl, MD, Professor for Medical Oncology at the Washington University School of Medicine in St. Louis. “With the impressive activity already observed at low doses, we look forward to continuing this study to further identify the maximum tolerable dose and provide a preliminary assessment of its single-agent antitumor activity and toxicity profile. The promising overall response seen in specific non-Hodgkin lymphoma subtypes leads us to also further evaluate the drug candidate in diffuse large B-cell lymphoma.”
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