Keytruda study (pembrolizumab) in DNA mismatch repair (MMR) deficiency for colorectal cancer-Merck inc.

Merck has announced results from the first study evaluating the correlation of benefit with an immunotherapy based on DNA mismatch repair (MMR) deficiency, a well-established form of genetic instability in many cancers characterized by the loss of function of the MMR pathway. The Phase II study, led by researchers from Johns Hopkins Kimmel Cancer Center, evaluated Merck’s anti-PD-1 therapy, Keytruda (pembrolizumab), in 48 evaluable, heavily pre-treated patients with advanced colorectal cancer and other solid tumors. In the colorectal cancer group with MMR-deficient tumors, an objective response rate (ORR) of 62 percent was observed (n=8/13). In contrast, no responses were observed in the colorectal cancer group with MMR-proficient tumors (n=0/25). At the time of analysis, the median progression-free survival (PFS) and overall survival (OS) were not reached in the MMR-deficient colorectal cancer group. These data, featured in the American Society of Clinical Oncology (ASCO) Press Program and published in the New England Journal of Medicine, were presented in an oral session by Dr. Dung Le on Saturday, May 30 at the 2015 ASCO Annual Meeting in Chicago (Abstract #LBA100).

Based on the encouraging results of this early study, Merck will initiate a registrational Phase II study (KEYNOTE-164) to evaluate the efficacy and safety of Keytruda based on mismatch repair status in locally advanced unresectable or metastatic (Stage IV) colorectal cancers. This study is expected to begin enrolling patients in mid-2015.

See- "PD-1 Blockade in Tumors with Mismatch-Repair Deficiency."- Dung T. Le, M.D., Jennifer N. Uram, Ph.D., Hao Wang, Ph.D., Bjarne R. Bartlett, B.S.,et.,al.-May 30, 2015DOI: 10.1056/NEJMoa1500596.