Regulatory Decision Summary for Blincyto

Clinical evidence was provided for expanding the indication for the treatment of adults with R/R B-cell precursor ALL to include adults with Ph-positive R/R B-cell precursor ALL. In the single arm study of Ph-positive patients (study 20120216), the primary endpoint was the rate of complete remission within the first 2 cycles of therapy, including those with full and incomplete hematological recovery from therapy. A key secondary endpoint was the duration of the complete response. Of the 45 patients in the full analysis set (all enrolled patients), 16 subjects (35.6%) achieved a complete response. The median time to hematological relapse in patients achieving a complete response in the first 2 cycles was 6.7 months.

In this study, serious treatment-related adverse events and higher grade (i.e., grade ≥3) adverse events occurred in 26.7% and 44.4% of patients, respectively. The most common treatment-emergent adverse events were febrile neutropenia, sepsis, tremor, and device-related infection. Neurotoxic adverse events occurred in 46% of patients, among whom 14.3% experienced grade ≥3 severity. Among the events of particular interest, cytokine release syndrome was most common (8.9%) but no cases were grade ≥3 in severity. Overall, no new safety problems were reported and the number and severity of adverse events among these Ph-positive patients were similar to adverse events reported in the randomized TOWER trial and in the single arm supportive trial MT103-211, both of which enrolled only Ph-negative patients. While adverse events can be frequent and sometimes severe, they can be generally managed successfully with close monitoring and early therapeutic intervention.

Based on the demonstrated benefit and acceptable safety, a Notice of Compliance (NOC) was issued to Blincyto for the treatment of adults with refractory or recurrent B-cell precursor ALL regardless of Philadelphia chromosome status.