Interim results from an ongoing Phase I, open label, dose-escalating study evaluating ADCT-301, being developed by ADC Therapeutics for the treatment of relapsed or refractory Hodgkin’s and non-Hodgkin’s lymphoma, presented  at the 14th International Conference on Malignant Lymphoma (ICML), held June 14 – 17, 2017 the Lugano Convention Centre, Palazzo dei Congressi, in Lugano, Switzerland, confirms  favorable tolerability and efficacy. [1]

The results were included in a poster showing tolerability, safety, pharmacokinetics and efficacy in patients with relapsed or refractory Hodgkin’s and non-Hodgkin’s lymphoma (r/r HL/NHL).

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.

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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.

Trial results
The results included data from 37 extensively pretreated patients with a median age of 46 years, a median treatment duration of 43 days and 2 treatment cycles. Among all patients enrolled at the time of the data cutoff for presentation and evaluable for safety, the most common treatment emergent adverse events have been related to skin and decreased blood counts.

The overall response rate for evaluable patients with HL treated with doses 30μg/kg was 38.5% while 8 of 25 (32%) efficacy evaluable patients at all dose levels with HL and NHL have achieved stable disease as their best response. The researchers confirmed that ADCT-301 was well tolerated and toxicities manageable. Dose escalation continues.

Pyrrolobenzodiazepine-based ADC
ADCT- 301 is a novel antibody-drug conjugate (ADC) composed of HuMax®-TAC (licensed from Genmab), a monoclonal antibody directed against CD25 conjugated to ADC Therapeutics’ highly potent proprietary pyrrolobenzodiazepine (PBD)-dimer toxin. Once bound to a CD25-expresing cell, ADCT-301 is internalized into the cell where enzymes release the PBD- based payload.

CD25 is expressed in a wide range of hematological malignancies, including certain forms of lymphomas and leukemias, while its expression in healthy organs is restricted. This makes CD25, as a target, attractive.

“The results seen in this early analysis are impressive for these patients with relapsed or refractory Hodgkin’s and non-Hodgkin’s lymphoma have been heavily pre-treated,’ noted Jay Feingold, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics.

“These data, combined with the positive results we have seen in preclinical studies continue to highlight what we believe to be the significant potential of our ADC technology platform based on PBD-warheads,” Feingold added.

“Patients with multiply relapsed or refractory Hodgkin’s or non-Hodgkin’s lymphoma have limited treatment options. These early findings are very encouraging as they demonstrate a clear clinical benefit even at low doses for patients who failed, or are intolerant to any established therapy,” explained principal investigator Steven M. Horwitz, Medical Oncologist at Memorial Sloan Kettering Cancer Center in New York City.

“We look forward to continuing this study to further identify the maximum tolerable dose of ADCT-301 and provide a preliminary assessment of its single-agent anti-tumor activity and toxicity profile,” Horwitz added.

In addition to the ongoing Phase I trial, ADCT-301 is currently being evaluated in an ongoing Phase I clinical trial in Acute Myeloid Leukemia (AML) and 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.