New Genentech breast cancer drug shows late stage trial success
SOUTH SAN FRANCISCO, Calif.—Genentech, a member of the Roche Group, recently announced top-line results of EMILIA, the first randomized Phase III study of trastuzumab emtansine (T-DM1), showing that people who received trastuzumab emtansine lived significantly longer without their disease getting worse (progression-free survival) compared to those who received lapatinib plus Xeloda (capecitabine).
The study enrolled people with HER2-positive metastatic 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. According to Genentech, the safety profile of trastuzumab emtansine was consistent with that seen in previous studies.
Trastuzumab emtansine is an investigational medicine known as an antibody-drug conjugate (ADC). It is comprised of the antibody trastuzumab and the chemotherapy DM1 attached together using a stable linker. It is designed to target and inhibit HER2 signaling and deliver the chemotherapy directly inside HER2-positive cancer cells. According to Genenetch, trastuzumab emtansine "reinforces Roche's personalized healthcare approach of developing targeted medicines to fight cancer."
"Trastuzumab emtansine represents a new approach for the treatment of people with HER2-positive breast cancer that comes from our decades of research on the HER pathway," said Dr. Hal Barron, chief medical officer and head of Global Product Development. "We are excited about the EMILIA results because trastuzumab emtansine is our first antibody-drug conjugate and it may help people who still need more treatment options for this aggressive disease. We will work to submit these data to regulatory authorities as quickly as possible."
Based on these findings, Genentech plans to submit a Biologics License Application for trastuzumab emtansine to the U.S. Food and Drug Administration this year for HER2-positive mBC. In addition, Roche plans to submit a Marketing Authorization Application to the European Medicines Agency this year for the same indication. Genentech licenses technology for trastuzumab emtansine under an agreement with ImmunoGen Inc.
As Luke Timmerman noted at Xconomy.com, "Even though Genentech is responsible for development, and will keep the vast majority of product revenues for itself, today's result is an important moment for ImmunoGen. The company stands to collect a 'mid-single digit' percentage royalty on worldwide sales from T-DM1, because of its contribution to help link the antibody to the toxin. ImmunoGen has no products of its own on the market, and the approval of T-DM1 would provide a significant percentage from a potential multi-billion dollar seller."
EMILIA (TDM4370g/BO21977) is an international, Phase III, randomized, open-label study comparing trastuzumab emtansine alone to lapatinib in combination with Xeloda in 991 people with HER2-positive mBC whose disease progressed after initial treatment with Herceptin and a taxane chemotherapy.
The co-primary efficacy endpoints of the study are progression-free survival (as assessed by an independent review committee) and overall survival. Other study endpoints include safety profile, one-year and two-year survival rates, progression-free survival as assessed by investigator, overall response rate, duration of response and quality of life.
In addition to EMILIA, there are two ongoing Phase III studies of trastuzumab emtansine. MARIANNE is comparing three different regimens (trastuzumab emtansine alone, trastuzumab emtansine plus pertuzumab, and Herceptin plus a taxane chemotherapy) in people with HER2-positive metastatic breast cancer who have not been previously treated for their metastatic disease. TH3RESA is comparing trastuzumab emtansine to physician's choice of treatment in people with HER2-positive metastatic breast cancer who have already received both Herceptin and lapatinib.
According to Genentech, "Building on the results of trastuzumab emtansine studies to date, Roche/Genentech have approximately 30 ADCs in the pipeline."