MedImmune files IND for MT103 to treat lymphomas, triggers milestone payment to Micromet

By E. Janene Geiss

Philadelphia, Aug. 21 - MedImmune, Inc. and Micromet, Inc. announced Monday that MedImmune has filed an Investigational New Drug application with the Food and Drug Administration for MT103, also known as MEDI-538, for the treatment of patients with B-cell-derived non-Hodgkins lymphoma 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, according to a company news release.

"The specific targeting of T-cells against tumor 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," Dirk Reitsma, vice president of clinical development for oncology at MedImmune, said in the release.

Pending FDA review, MedImmune said it plans to begin dosing patients soon in a phase 1 study designed to extend the clinical progress made to date in European studies by its partner, Micromet.

MedImmune and Micromet AG, a wholly owned subsidiary of Micromet, Inc., entered an agreement in 2003 to jointly develop MT103.

Under the collaboration agreement, Micromet said it will receive a milestone payment from MedImmune triggered by the filing.

In MedImmune's planned phase 1 open-label, single-arm, dose-escalation trial in the United States, investigators will assess the safety, tolerability and antitumor activity of continuous intravenous infusion of MT103 in patients with B-cell-derived non-Hodgkin's lymphoma 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, officials said.

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 non-Hodgkin's lymphoma.

In this study, about 20 patients have been treated over longer dosing periods than in previous studies. In the first three cohorts of patients in this trial (who received doses of 0.5 up to 5 micrograms per meter squared over 24 hours for four to eight weeks), no dose limiting toxicities have been observed.

Evaluation of a fourth dose level, which is 15 micrograms per meter squared over 24 hours, is 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, officials said.

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 tumor response and two patients showed partial tumor responses, according to standardized Cheson criteria. These preliminary data were presented at the 11th Congress of the European Hematology Association in June 2006, officials said.

MT103 is a BiTE molecule being developed as a potential treatment for certain types of B-cell lymphomas.

In February 2006, the FDA approved an orphan-drug designation for MT103 for the treatment of indolent B-cell lymphoma, excluding chronic lymphocytic leukemia and non-Hodgkin's lymphoma with central nervous system involvement. MT103 also received orphan-drug designation from the European Agency for the Evaluation of Medicinal Products for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia.

MedImmune is a Gaithersburg, Md., biopharmaceutical company focused on infectious diseases, cancer and inflammatory diseases.

Micromet is a Carlsbad, Calif., biopharmaceutical company.

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