Phase I study of M6620 (VX-970, berzosertib) in combination with cisplatin and XRT in patients with locally advanced head and neck squamous cell carcinoma

M6620 is a highly potent and selective ATP-competitive ATR inhibitor. It showed strong synergy with cisplatin and radiation in preclinical cancer models. The significant vulnerability to ATR inhibition by cancer cells harboring inactivating p53 mutations provided a rationale to test the safety of M6620 along with definitive chemoradiation in Head and Neck Squamous Cell Carcinoma (HNSCC) where such alterations are common.