The US Food and Drug Administration (FDA) has issued a refuse-to-file letter for accelerated approval of Genentech antibody-drug conjugate trastuzumab-DM1 (T-DM1).

Genentech will continue with its ongoing Phase III registrational T-DM1 trial and now expects to submit a new T-DM1 biologic licence application in mid-2012.

A biologic licence application submitted in July 2010 requested accelerated approval for T-DM1 based on the results of a single-arm Phase II study, which showed T-DM1 shrank tumours in one-third of women with advanced HER2-positive breast cancer who had received on average seven prior medicines, including two HER2-targeted medicines.

However, the FDA declared 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 submit data from the amended Phase III randomised EMILIA study to the FDA to support its new biologic licence application.