Phase I study of novel antibody-drug conjugate ADCT-402

Since the end of March 2017, 7 patients have been recruited into the Phase I study sponsored by ADC Therapeutics (Lausanne, Switzerland) of a novel antibody drug conjugate ADCT-402 in patients with relapsed/refractory non-Hodgkin lymphoma. This molecule targets CD19 on the surface of B-cells and carries a pyrrolobenzodiazepine payload, a potent minor DNA groove binder. Toxicity includes myelosuppression, fatigue, oedema and photosensitive skin rash but overall ADCT-402 has been well tolerated and partial and complete responses have been observed with two of the patients so far proceeding towards allogeneic transplantation. An abstract has been submitted to the December 2017 ASH meeting, Atlanta, GA. Recruitment continues, with another four Christie patients under active consideration.

This study with ADCT-402 is the latest stage of a programme of research with antibody-drug conjugates in lymphoma. Related early phase studies include brentuximab vedotin in anaplastic large cell lymphoma, by Professor Illidge, and in Hodgkin lymphoma, by Professor Radford. Radford was one of two international experts who presented data to the European Medicines Agency, leading to the award of a provisional license in 2012. Subsequently, evidence was presented to NICE which recently approved the use of brentuximab vedotin in patients with recurrent disease after autologous transplantation.

Manchester has also led an NCRI portfolio investigator-initiated Phase II study of brentuximab vedotin in frail elderly patients with previously untreated Hodgkin lymphoma (BREVITY), the results of which were presented orally at the ICML meeting in Lugano, June 2017. Translational aspects include correlation of PET response and clinical outcomes with circulating biomarkers of response, analysed at the Stoller Centre in Manchester with the aim of replacing expensive and time consuming scans with a simple blood test.