The trial is specifically evaluating the safety and tolerability of a continuous infusion of MT103 over a 4- to 8-week period at escalating dose levels. The data were presented at the 11th Congress of the European Hematology Association.
So far, 19 patients with a median number of four previous lines of therapy have been included. In the first three cohorts (0.5 up to 5 mg/m2/24 h), no dose limiting toxicities have been observed. Evaluation of dose level 4 (15 mg/m2/24h) is currently ongoing.
Pharmacodynamic effects have been observed at 5 and 15 mg/m2/24 h 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 mg/m2/24 h 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.
The most common adverse events of grade 3 or higher were lymphopenia (63%), leukopenia (47%), neutropenia and enzyme abnormality (both 16%).
“These preliminary clinical data are encouraging. In particular, the observation of confirmed clinical responses after single-agent treatment with very low doses of MT103/MEDI-538 in this late-stage patient population shows the therapeutic potential of the BiTE platform,” commented Dr Dirk Reitsma, vice president of Clinical Oncology at MedImmune.
MT103 is a recombinant single-chain bispecific antibody derivative out of Micromet’s BiTE platform targeting the CD19 antigen, which is uniquely expressed on B cells. The BiTE molecule is being co-developed by Micromet and MedImmune for the treatment of B cell-derived lymphomas and leukemias.