T-DM1 is an armed antibody (aka antibody drug conjugate, ADC) which contains a potent chemotherapy drug maytansine linked via a linker to the Her2 receptor specific drug trastuzumab (Herceptin). T-DM1 has an advantage over trastuzumab because it allows targeting and killing of cancer cells with lower Her2 expression. The conjugation technology is licenced from ImmunoGen
About EMILIA (TDM4370g/BO21977) Study
- Phase 3 open-label trial
- Patientswith Her2-positive metastatic breast cancer previously treated with trastuzumab and taxane-based chemotherapy whose disease had worsened.
- Total participants = 991.
- Trastuumab emtansine arm: T-DM1 alone 3.6 mg/kg every three weeks.
- Lapatinib and capecitabine arm: 1250 mg lapatinib daily and 2000 mg/m2 Xeloda on days 1-14 every three weeks.
- Endpoints: "The co-primary efficacy endpoints of the study are PFS (as assessed by an independent review committee) and OS. Other study endpoints include safety profile, one-year and two-year survival rates, PFS as assessed by investigator, overall response rate, duration of response and quality of life." -- from Roche press release
Two related phase 3 trials:
- MARIANNE is comparing three different regimens (trastuzumab emtansine alone, trastuzumab emtansine plus pertuzumab, and Herceptin plus a taxane chemotherapy) in people with HER2-positive mBC who have not been previously treated for their metastatic disease.
- TH3RESA is comparing trastuzumab emtansine with physician's choice of treatment in people with HER2-positive metastatic breast cancer who have already received both Herceptin and lapatinib.
The regulatory filing are planned this year -- Marketing Authorisation Application to the European Medicines Agency (EMA) by Roche for use in HER2-positive metastatic breast cancer, and Biologics License Application to U.S. FDA.
San Antonio Breast Cancer Symposium 2011: Clinical Trials Report. December 8, 2011.