A breast cancer cell Credit: NCI/Science Photo Library

Genentech released the results from the first phase 3 trial of T-DM1 (trastuzumab emtansine) at the annual meeting of the American Society of Clinical Oncology (ASCO) in June. The data from the S. San Francisco, California–firm's trial in HER2-positive breast cancer impressed oncologists and provided a big boost for the burgeoning field of antibody-drug conjugates (ADCs) (Nat. Biotechnol. 29, 297–298, 2011). “This was the most compelling example to date of an ADC in cancer therapy,” says Louis Weiner of Georgetown University in Washington, DC. “Other investigators and companies will now go back to their freezers and see what they have in stock—they may have monoclonal antibodies and drugs that may be linked to go after many different targets in many different cancers.” T-DM1 combines Genentech's blockbuster HER2-targeted monoclonal antibody Herceptin (trastuzumab) with antimitotic cytotoxin N2′-deacetyl-N2′-(3-mercapto-1-oxopropyl)-maytansine (termed DM1), using linker technology from ImmunoGen of Waltham, Massachusetts. The results show T-DM1 met its co-primary progression-free survival endpoint in women with HER2-positive metastatic breast cancer whose disease had progressed after treatment with Herceptin. The 991-patient EMILIA study compared T-DM1 to the small-molecule HER2-targeted drug Tykerb (lapatinib) plus Xeloda (capecitabine) chemotherapy. Median progression-free survival was 9.6 months and 6.4 months, respectively. Although the overall survival analysis did not yet reach statistical significance, two-year survival was 65.4% for T-DM1 and 47.5% for control. “If this trend continues, median overall survival with T-DM1 will be at least a year longer than with control,” says Weiner. Severe adverse events were less frequent with the ADC than with control. Genentech and Roche plan to file this year for US and European approval for T-DM1 in HER2-positive metastatic breast cancer. An ongoing phase 3 trial in first-line metastatic breast cancer is comparing T-DM1 alone, T-DM1 plus Genentech's recently approved Perjeta (pertuzumab), and Herceptin combined with taxane chemotherapy. Seattle Genetics, which last year secured approval for its ADC Adcetris (brentuximab vedotin) to treat relapsed or refractory Hodgkin's lymphoma and anaplastic large cell lymphoma, is testing it in four ongoing and planned phase 3 trials in earlier-stage Hodgkin's lymphoma and T-cell lymphoma, and in relapsed cutaneous T-cell lymphoma. Pfizer is testing its ADC inotuzumab ozogamicin in a phase 3 trial in aggressive non-Hodgkin's lymphoma. In June, Merck of Whitehouse Station, New Jersey, entered a deal worth up to $288 million with Ambrx to develop ADCs.