1991; Baselga et al. 1998; Pegram CONFIDENTIAL Page 7 of 102 Protocol: HERCEPTIN® + E75/GM-CSF Version 3.1 ML25749 05 March 2017 et al. 1997). Given this promising preclinical data, Herceptin was tested in the clinic both as a single agent and in combination with chemotherapy. 1.3 HERCEPTIN CLINICAL EXPERIENCE The clinical benefit of Herceptin in women with metastatic breast cancer has been demonstrated in two pivotal studies. A large Phase II trial (H0649g) assessed the activity of Herceptin as a single agent in 222 women with HER2 overexpressing metastatic breast cancer with progressive disease after one or more chemotherapy regimens (Cobleigh et al. 1999).