Trastuzumab-DM1 (T-DM1) consists of our DM1 cell-killing agent attached to the HER2-binding antibody, trastuzumab, developed by Genentech (a member of the Roche Group) using our linker and methods of attachment. T-DM1 is in global development by Roche under a collaboration agreement between ImmunoGen and Genentech.

T-DM1 is being developed for the treatment of all stages of HER2+ metastatic breast cancer (MBC):

Development for 3rd-line Use

In early July 2010, Genetech/Roche announced it had submitted a marketing application to the US FDA for accelerated approval of T-DM1 to treat patients with HER2+ MBC who had previously received multiple chemotherapies and HER2-targeted medicines.* The basis of this submission was the Phase II trial that was presented at a breast cancer symposium in December 2009. In late August 2010, Genentech/Roche announced that the FDA had refused to file this marketing application on the grounds that it did not meet the standard for accelerated approval. At that time, Genentech/Roche also conveyed its plans to apply for 3rd-line use when it applies for approval of T-DM1 for 2nd-line use, which it expects to do in mid-2012.

Development for 2nd-line Use

Roche expects to use its Phase III trial (EMILIA) evaluating T-DM1 for 2nd-line** use to apply for marketing approval of T-DM1 in mid-2012 in the US and Europe. This randomized trial began in February 2009 and compares T-DM1 – used as a single agent – to Tykerbâ (lapatinib) plus Xelodaâ (capecitabine).

Development for 1st-line Use

Roche expects to use its Phase III trial (MARIANNE) evaluating T-DM1 for 1st-line use to apply for marketing approval of T-DM1 for this application at a timepoint after 2013 (the farthest out that Roche makes projections related to regulatory submissions) in the US and Europe. This randomized trial began in July 2010 and compares T-DM1 – used as a single agent – to Herceptinâ (trastuzumab) plus a taxane (docetaxel or paclitaxel)

A Phase II trial evaluating T-DM1 for 1st-line use has completed patient enrollment, and interim data will be reported at the European Society of Medical Oncology (ESMO) meeting being held Oct. 8-12, 2010 in Milan, Italy. This trial compares T-DM1, given as a single agent, to Herceptinâ (trastuzumab) plus Taxotereâ (docetaxel).

Development for Treatment of Early Stage HER2+ Breast Cancer

Genentech has disclosed that trials to evaluate T-DM1 for early stage HER2+ breast cancer (adjuvant use) are being considered.

Data from earlier-stage Phase I and Phase II clinical trials also have been reported.

*Patients must have had prior treatment with at least two lines of anti-HER2 therapy in the metastatic setting, and must have received an anthracycline, a taxane, trastuzumab, lapatinib and capecitabine in the neoadjuvant, adjuvant, locally advanced or metastatic setting.
**Patients must have received prior treatment that included both a taxane (alone or in combination with another agent) and trastuzumab in the adjuvant, locally advanced or metastatic setting.

Tykerbâ is a registered trademark of GlaxoSmithKline plc.
Xelodaâ is a registered trademark of Roche.
Herceptinâ is a registered trademark of Genentech, a member of the Roche Group.
Taxotereâ is a registered trademark of sanofi-aventis.