The objective response rate for patients treated with T-DM1 was 47.8%, compared to 41.4% for patients treated with Herceptin plus chemotherapy, with a minimum of 5.9 months of patient follow-up. Longer follow-up is required for analysis of progression-free survival (PFS) – the primary endpoint of the study – and for final, mature objective response rate data. Final PFS data are expected to be available in 2Q 2011.
Of particular note, the incidence of more serious side effects (Grade 3 and higher) reported with T-DM1 was approximately half of that reported with trastuzumab plus docetaxel (37% vs. 75%, respectively), with no increased risk of cardiotoxicity. There were no new safety-signals reported with T-DM1 in this trial compared with earlier T-DM1 clinical studies.
The most common adverse events (all grades) in the Herceptin plus docetaxel arm of the study were alopecia (66.2% compared to 1.5% for the T-DM1 arm), neutropenia (57.4% vs. 7.5%) and diarrhea (45.6% vs. 10.4%). The most common adverse events in the T-DM1 arm of the study were nausea (47.8% vs. 39.7% for the Herceptin plus docetaxel arm), fatigue (46.3% vs. 46.2%) and temperature increase (35.8% vs. 20.6%).
This early analysis supports further investigation of T-DM1 for first-line treatment of HER2+ metastatic breast cancer. In July 2010, Roche initiated a Phase III trial, MARIANNE, to assess T-DM1 further for this use. MARIANNE compares both T-DM1 alone and T-DM1 used in combination with pertuzumab to Herceptin used in combination with a taxane in patients with advanced HER2+ breast cancer not previously treated for advanced disease.
T-DM1 consists of ImmunoGen’s DM1 cancer cell-killing agent attached using the Company’s linker and methods of attachment to the HER2-targeting antibody, trastuzumab, developed by Genentech. T-DM1 is in Phase III testing for second-line and first-line treatment of HER2+ metastatic breast cancer (EMILIA and MARIANNE, respectively). A Phase II trial to evaluate the cardiac event rate and safety of T-DM1 in the neoadjuvant/adjuvant setting is scheduled to begin in 4Q2010.
About ImmunoGen’s Targeted Antibody Payload (TAP) Technology
The Company’s TAP technology uses tumor-targeting antibodies to deliver one of ImmunoGen’s highly potent cancer-cell killing agents (e.g., DM1, DM4) specifically to tumors. The Company’s proprietary cytotoxic agents are many-fold more potent than standard chemotherapeutics and were developed by ImmunoGen specifically for targeted delivery to tumors. The Company also has engineered linkage technology that keeps the cancer-cell killing agent attached to the antibody until it reaches the tumor cells and then controls the release of the agent inside the cell. Currently, seven TAP compounds are in clinical testing, with 3-4 more expected to enter the clinic in 2011.
About ImmunoGen, Inc.
ImmunoGen, Inc. develops targeted anticancer therapeutics using its expertise in cancer biology, monoclonal antibodies and the creation and attachment of potent cancer cell-killing agents. The Company’s TAP technology uses engineered antibodies to deliver one of ImmunoGen’s proprietary cancer-cell killing agents specifically to tumor targets. Product candidates are in development through the Company’s own product programs and through ImmunoGen’s collaborations with Amgen, Bayer Schering Pharma, Biogen Idec, Biotest, Genentech and sanofi-aventis. The most advanced compound using ImmunoGen’s TAP technology, T-DM1, is in Phase III testing through the Company’s collaboration with Genentech.