MedImmune, Inc has filed an investigational new drug application (IND) with the US Food and Drug Administration (FDA) for MT103 (also known as MEDI-538) for the treatment of patients with B-cell-derived non-Hodgkins lymphoma (NHL) not eligible for curative therapy. MT103 is a recombinant single chain bispecific T-cell engager, or BiTE, molecule. It targets the CD19 antigen, which is uniquely expressed on B cells.
"The specific targeting of T-cells against tumour cells by MT103 represents a new approach to cancer therapy with potential benefits for patients suffering from certain lymphomas and leukemias, particularly those who have not responded to previous therapies,'' commented Dirk Reitsma, MD, vice president, clinical development, oncology, MedImmune, Inc. "Pending FDA review, we plan to begin dosing patients soon in a phase 1 study designed to extend the clinical progress made to date in European studies by our partner, Micromet.''
MedImmune and Micromet AG, a wholly owned subsidiary of Micromet, Inc., entered an agreement in 2003 to jointly develop MT103. Under the terms of the companies' collaboration agreement, Micromet will receive a milestone payment from MedImmune triggered by the IND filing.
In MedImmune's planned phase 1 open-label, single-arm, dose escalation trial in the US, investigators will assess the safety, tolerability and anti tumour activity of continuous intravenous (IV) infusion of MT103 in patients with B-cell-derived NHL who have not responded to or have become refractory to previous therapies. Other endpoints include MT103's pharmacokinetics, pharmacodynamics, and immunogenicity as well as exploration of the molecule's mechanism of action. Doses will be given for a four-week period, with an option for an additional four weeks of therapy if disease improvement or stabilization is observed.
"We look forward to extending the clinical trial program for MT103 into the US,'' said Carsten Reinhardt, senior vice president, clinical development, Micromet, Inc. "Given the encouraging interim results of the ongoing European phase 1 trial with responses seen in an extensively pretreated patient population, we hope to substantiate the therapeutic potential of this molecule.''
The ongoing phase 1 trial being conducted by Micromet in Germany, is investigating the safety and tolerability of a continuous infusion of MT103, over a four to eight week period at escalating dose levels in patients with relapsed, indolent B-cell NHL. In this study, approximately 20 patients have been treated to date over longer dosing periods than in previous studies. No dose limiting toxicities have been observed. Evaluation of a fourth dose level, which is 15 micrograms per meter squared over 24 hours, is currently ongoing. Pharmacodynamic effects have been observed at 5 and 15 micrograms per meter squared over 24 hours with complete depletion of malignant B cells as well as significant T cell expansion in the majority of patients. Three out of five patients receiving 15 micrograms per meter squared over 24 hours of MT103 for at least two weeks showed clinical responses assessed by central radiology. One patient had a complete tumour response and two patients showed partial tumour responses according to standardized Cheson criteria. These preliminary data from the ongoing European phase 1 trial of MT103 were presented, at the 11th Congress of the European Hematology Association in June 2006.