MM-151 Oligoclonal anti-EGFR antibody combination Treatment of colorectal cancer Treatment of non-small cell lung cancer Treatment of head and neck cancer

摘要

MM-151 is a third-generation epidermal growth factor receptor (EGFR) inhibitor comprising an oligoclonal combination of three fully human IgG1 antibodies that target distinct nonoverlapping EGFR epitopes to inhibit binding of all EGFR ligands at subnanomolar affinity. There is a significant redundancy in the ERB receptor tyrosine kinase signaling pathways, which are a well-established target for anticancer therapies. Such redundancy, in addition to receptor mutation in pretreated patients, is a significant problem for drug-resistant tumors, particularly in patients with metastatic colorectal cancer (mCRC). Preclinical studies have shown that MM-151 uniquely downregulates the EGFR, inhibits binding of all low-and high-affinity ligands to the receptor, and activates immune effector responses. In addition, MM-151 has a binding profile that is not affected by acquired EGFR mutations. Preliminary clinical studies have indicated that MM-151 monotherapy or MM-151 plus irinotecan was well tolerated and showed promising efficacy in patients with mCRC.