FDA has sent Genentech a refuse to file (RTF) letter with regard to the BLA for accelerated approval of trastuzumab-DM1 (T-DM1) in metastatic breast cancer. The agency stated that the T-DM1 trials did not meet the standard for accelerated approval because all available treatment choices approved for metastatic breast cancer, regardless of Her2 status, had not been exhausted in the study population.
Genentech will continue with its ongoing Phase III trial, known as EMILIA, and expects to submit a new BLA in mid-2012. The EMILIA study compares T-DM1 to lapatinib in combination with capecitabine in people with advanced, Her2-positive breast cancer whose disease has worsened after receiving initial treatment.
The BLA submitted for T-DM1 in July 2010 requested accelerated approval based on the results of a single-arm Phase II study. It showed that T-DM1 shrank tumors in one-third of women with advanced Her2-positive breast cancer who had received on average of seven prior medicines including two Her2-targeted medicines.
T-DM1 consists of ImmunoGen’s DM1 cancer-cell killing agent attached to Genentech’s Her2-targeting antibody, trastuzumab, using ImmunoGen’s linker and methods of attachment. T-DM1 is in global development by Roche under a collaboration agreement between Genentech and ImmunoGen.