MT103, BiTE antibody, enters phase II testing for ALL

BETHESDA, Maryland—Micromet, Inc. has announced that the Paul-Ehrlich Institute, Langen, Germany, has approved an Investigational Medicinal Product Dossier for the conduct of a phase II clinical trial testing MT103 in patients with acute lymphoblastic leukemia.

The German trial will test whether MT103 can remove residual tumor cells and thereby convert patients who are minimal residual disease (MRD) positive to MRD-negative status, with an improved time to relapse.

Targets CD19

MT103 is a BiTE antibody targeting the CD19 antigen, which is expressed on most malignant B lymphoma cells. Although CD19 is widely expressed in ALL, no antibody against this tumor-associated antigen target has been developed thus far, the company said.

MT103 is also being evaluated in an ongoing phase I clinical trial in Europe in patients with non-Hodgkin's lymphoma.

Micromet and MedImmune, a subsidiary of AstraZeneca, are currently developing MT103 (also known as MEDI-538). Under a 2003 agreement, Micromet granted MedImmune exclusive rights for MT103 for North America.

BiTE (bi-specific T-cell engager) antibodies (see Figure) are designed to direct the body's cytotoxic cells against tumor cells. BiTE antibodies have been shown to induce an immunological synapse between a T cell and a tumor cell in the same manner as observed during physiological T-cell attacks, according to Micromet. These cytolytic synapses enable the delivery of cytotoxic proteins from T cells into tumor cells, ultimately inducing apoptosis in the tumor cell.

In the presence of BiTE antibodies, T cells have been shown to serially eliminate tumor cells, which explains the activity of BiTE antibodies at very low concentrations and at very low ratios of T cells to target tumors cells, the company said.

Consolidation therapy

"The upcoming phase II clinical trial in ALL is an important step to establish the activity of MT103 in aggressive B-cell leukemias and lymphomas," said Carsten Reinhardt, MD, PhD, Micromet's senior vice-president and chief medical officer. "Investigating the effect of MT103 on minimal residual disease may open a highly promising new treatment concept in these diseases, that is, consolidation therapy with a BiTE antibody after initial treatment with a chemotherapeutic regimen."