First Clinical Data from ADCT-402 Demonstrates Encouraging Antitumor Activity in r/r non-Hodgkin Lymphoma
Published on 16th June
The first clinical data from an ongoing Phase I clinical trial evaluating ADCT-402 for the treatment of relapsed or refractory non-Hodgkin’s lymphoma has been presented at the 14th International Conference on Malignant Lymphoma (ICML), held June 14 – 17, 2017 in Lugano, Switzerland. 
ADCT-402, a novel antibody-drug conjugate or ADC, is composed of a humanized monoclonal antibody that binds to human CD19, conjugated to a highly potent proprietary pyrrolobenzodiazepine (PBD) dimer toxin. The drug is being developed by ADC Therapeutics.
The PBD-based payload has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death.
CD19 clinically validated target, highly expressed in a wide range of B-cell hematological tumors, including certain forms of lymphomas and leukemias, while its expression in healthy tissues is restricted.
Lymphoma is a cancer that begins in cells of the immune system, in particular in the lymph system. The lymph is rich in lymphocytes, a type of white blood cells that help the body fight off infections and other diseases. Lymphoma develops when lymphocytes become cancerous which can occur in both children and adults. The two main types of lymphomas are Hodgkin lymphoma (HL) and non-Hodgkin lymphomas (NHL), and are differentiated by the type of lymphocytes affected and their appearance under the microscope.
According to the National Cancer Institute around 72,000 new people are diagnosed with non-Hodgkin lymphoma in the United States and around 9,000 new people are diagnosed with Hodgkin lymphoma.
Interim trial results
The 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’s lymphoma (r/r NHL) were reported. Data were presented from 62 evaluable patients with a median age of 67 years and 3 previous therapies.
Treatment emergent adverse events
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 or TEAEs being fatigue, neutropenia and thrombocytopenia which have been treated symptomatically and, in some cases, with dose delays, reductions and discontinuation. The overall response rate with doses 120μg/kg was 61% in the total patient population and 57% in patients with relapsing or refractory diffuse large B-cell lymphoma (DLBCL). The maximum tolerated dose has not yet been reached.
“These clinical data provide additional support for the efficacy and tolerability of ADCT-402, as well as of our ADC technology platform based on PBD-warheads,” noted Jay Feingold, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics.
“In preclinical studies the PBD 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’s lymphoma. We believe these findings reflect a strong path forward and we are looking forward to getting further results later this year,” he added.
“These early findings are very encouraging as they demonstrate a clear clinical benefit and manageable toxicity for patients who failed, or are intolerant to any established therapy” said principal investigator Brad Kahl, M.D. 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 anti-tumor activity and toxicity profile. The promising overall response seen in specific non-Hodgkin’s lymphoma subtypes leads us to also further evaluate the drug candidate in diffuse large B-cell lymphoma,” Kahl observed.
In addition to the ongoing Phase I trial, ADCT-402 is currently being evaluated in an ongoing Phase I clinical trial in Acute Lymphoblastic Leukemia (ALL). ADC Therapeutics has four PBD-based antibody drug conjugates in six ongoing Phase I clinical trials in the USA and in Europe.
Last editorial review: June 16, 2017
Featured Image: Lugano, Switzerland. Courtesy: © 2017 Lugano Convention Centre, Palazzo dei Congressi, in Lugano, Switzerland Used with permission.
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