The study enrolled people with HER2-positivemetastatic breast cancer who had previously received treatment with Herceptin(trastuzumab) and a taxane chemotherapy. Final results for overall survival(OS), a co-primary efficacy endpoint of EMILIA, are not yet mature. Accordingto Genentech, the safety profile of trastuzumab emtansine was consistent withthat seen in previous studies.
Trastuzumab emtansine is an investigationalmedicine known as an antibody-drug conjugate (ADC). It is comprised of theantibody trastuzumab and the chemotherapy DM1 attached together using a stablelinker. It is designed to target and inhibit HER2 signaling and deliver thechemotherapy directly inside HER2-positive cancer cells. According toGenenetch, trastuzumab emtansine "reinforces Roche's personalized healthcareapproach of developing targeted medicines to fight cancer."
"Trastuzumab emtansine represents a new approachfor the treatment of people with HER2-positive breast cancer that comes fromour decades of research on the HER pathway," said Dr. Hal Barron, chief medicalofficer and head of Global Product Development. "We are excited about theEMILIA results because trastuzumab emtansine is our first antibody-drugconjugate and it may help people who still need more treatment options for thisaggressive disease. We will work to submit these data to regulatory authoritiesas quickly as possible."
Based on these findings, Genentech plans to submita Biologics License Application for trastuzumab emtansine to the U.S. Food andDrug Administration this year for HER2-positive mBC. In addition, Roche plansto submit a Marketing Authorization Application to the European Medicines Agencythis year for the same indication. Genentech licenses technology fortrastuzumab emtansine under an agreement with ImmunoGen Inc.
As Luke Timmerman noted at Xconomy.com, "Even though Genentech is responsible fordevelopment, and will keep the vast majority of product revenues for itself,today's result is an important moment for ImmunoGen. The company stands tocollect a 'mid-single digit' percentage royalty on worldwide sales from T-DM1,because of its contribution to help link the antibody to the toxin. ImmunoGenhas no products of its own on the market, and the approval of T-DM1 wouldprovide a significant percentage from a potential multi-billiondollar seller."
EMILIA (TDM4370g/BO21977) is an international,Phase III, randomized, open-label study comparing trastuzumab emtansine aloneto lapatinib in combination with Xeloda in 991 people with HER2-positive mBCwhose disease progressed after initial treatment with Herceptin and a taxanechemotherapy.
The co-primary efficacy endpoints of the study areprogression-free survival (as assessed by an independent review committee) and overallsurvival. Other study endpoints include safety profile, one-year and two-yearsurvival rates, progression-free survival as assessed by investigator, overallresponse rate, duration of response and quality of life.
In addition to EMILIA, there are two ongoing PhaseIII studies of trastuzumab emtansine. MARIANNE is comparing three differentregimens (trastuzumab emtansine alone, trastuzumab emtansine plus pertuzumab,and Herceptin plus a taxane chemotherapy) in people with HER2-positive metastaticbreast cancer who have not been previously treated for their metastaticdisease. TH3RESA is comparing trastuzumab emtansine to physician's choice oftreatment in people with HER2-positive metastatic breast cancer who havealready received both Herceptin and lapatinib.
According to Genentech, "Building on the resultsof trastuzumab emtansine studies to date, Roche/Genentech have approximately 30ADCs in the pipeline."