The Food and Drug Administration has notified Roche that it will not accept the company’s application for an accelerated approval of trastuzumab-DM1 in advanced HER2-positive breast cancer.
Roche had filed for a fast-track review of T-DM1 in July, after meeting with the FDA in March to discuss such an application. The drug combines the anti-HER2 activity of trastuzumab (Herceptin) with the targeted intracellular delivery of DM1, a potent antimicrotubule agent. The DM1 component is licensed by ImmunoGen Inc.
In seeking the approval, Roche submitted results from a 110-patient single-arm phase II study. In that trial, one-third of women with advanced HER2-positive breast cancer had a tumor response. Results were presented at the 2009 San Antonio Breast Cancer Symposium.
Even though the women had received on average seven prior therapies, including HER2-targeted agents, the FDA told Roche that the trial did not meet the standard for accelerated approval because the patients had not exhausted all approved treatment options for metastatic breast cancer.
Roche said in a statement that it will continue with its phase III study, EMILIA, which compares T-DM1 to lapatinib (Tykerb) in combination with capecitabine (Xeloda) in advanced HER2-positive breast cancer. The study will evaluate overall survival and progression-free survival. Roche said it anticipated filing for approval in various nations, including the United States, in mid-2012.
“We firmly believe in the potential of T-DM1 as a novel HER2-targeted option and remain fully committed to its ongoing development,” said Dr. Hal Barron, Roche’s head of global development and chief medical officer, in a statement.
T-DM1 is being compared to trastuzumab in a phase II study in previously untreated advanced HER2-positive breast cancer as well. It is also in a phase III study, MARIANNE, where it is being compared with trastuzumab as a single agent or in combination with pertuzumab (Omnitarg) in previously untreated advanced HER2-positive breast cancer.