FDA Approval Sought for T-DM1

Genentech is seeking the FDA’s approval to offer trastuzumab emtansine (T-DM1) for the treatment of patients with HER2-positive metastatic breast cancer amid updated results from the pivotal EMILIA trial showing that the novel agent significantly improved overall survival (OS).

The company said it plans to launch an expanded access program in the United States to make T-DM1 available to selected patients while its Biologics License Application is pending.

T-DM1 is under study for patients with HER2-positive metastatic disease who have previously received trastuzumab (Herceptin), a monoclonal antibody that targets HER2, and taxane chemotherapy.

The novel therapeutic is among a new class of agents called antibody drug conjugates. T-DM1 combines the antibody trastuzumab with the cytotoxic emtansine using an MCC stable linker, thus disrupting HER2 signaling as well as transporting the cytotoxic agent directly into tumor cells.

In the phase III EMILIA trial, 991 patients were randomized 1:1 to receive either T-DM1 or standard therapy with the doublet regimen of capecitabine and lapatinib.

Results presented at the American Society of Clinical Oncology (ASCO) annual meeting in June indicated that the trial met its progression-free survival (PFS) endpoint, delaying disease progression for a median of 9.6 months, as compared with 6.4 months with the doublet regimen (hazard ratio [HR] = 0.650; 95% CI, 0.549—0.771; P <.0001).

At the time, the study had approached, but did not meet, its primary OS endpoint. The two-year OS for patients receiving T-DM1 was 65.4% versus 47.5% in the control arm (HR = 0.621; 95% CI, 0.475-0.813; P = .0005), according to presentations at ASCO.

These data did not meet a predetermined statistical goal for OS.

On Sunday, Genentech said in a press release that a confirmatory analysis of OS showed T-DM1 “crossed the prespecified boundary” in significantly extending survival compared with the doublet regimen. No further details were released. The company said the data would be presented at an upcoming medical meeting.

Meanwhile, participants in the control arm of the EMILIA study will be offered an opportunity to cross over to T-DM1, Genentech said.

While Genentech pursues FDA approvals, Roche will submit an application for marketing authorization for T-DM1 to the European Medicines Agency. Genentech is a member of the Roche Group.

As a result of the positive results achieved with T-DM1, Genentech and Roche have approximately 25 antibody drug conjugates in development. Genentech licenses the targeted antibody payload technology employed in T-DM1 from ImmunoGen, Inc.