ADC Therapeutics (ADCT), an oncology drug discovery and development company that specializes in the development of proprietary Antibody Drug Conjugates (ADCs) targeting major cancers, today announced that 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) in Lugano, Switzerland. ADCT-402 is a novel antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated to ADCT’s highly potent proprietary pyrrolobenzodiazepine (PBD) dimer toxin. CD19 is 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.
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’s lymphoma (r/r NHL) 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). 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 (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 (comprised of 42% complete response and 19% partial response). In patients with relapsing or refractory diffuse large B-cell lymphoma (DLBCL) the overall response rate was 57% (comprised of 43% complete response and 14% partial response). The maximum tolerated dose has not yet been reached.
Dr. Jay Feingold, Chief Medical Officer and Senior Vice President of Clinical Development at ADCT said: “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. 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.”
“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."
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.
See the video with Prof Brad Kahl’s comments under the following link: www.adctherapeutics.com/library/402.
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.
ADCT-402 is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD)-dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of certain CD19-expressing B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. ADCT-402 is being evaluated in two ongoing Phase Ia/Ib clinical trials in patients with relapsed or refractory B-cell lineage non-Hodgkin lymphoma and relapsed or refractory B-cell lineage acute lymphoblastic leukemia. (www.adct-402.com)
About ADC Therapeutics
Founded in 2012, ADC Therapeutics SA (ADCT) is an oncology drug development company that specializes in the development of proprietary antibody drug conjugates (ADCs) targeting major types of hematological malignancies and solid tumors. The Company’s ADCs are highly targeted biopharmaceutical drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with a novel class of highly potent pyrrolobenzodiazepine (PBD) based warheads via a chemical linker. Its three lead programs, ADCT-301, ADCT-402, and ADCT-502 are in five Phase I clinical trials in the USA and in Europe. ADCT enjoys strong relationships with world class partners, including AstraZeneca and its global biologics research and development arm, MedImmune. The Company is based in Lausanne, Switzerland and has operations in London, San Francisco and New Jersey (www.adctherapeutics.com).