Testing the Addition of M6620 (VX-970, Berzosertib) to Usual Chemotherapy and Radiation for Head and Neck Cancer

PRIMARY OBJECTIVES: I. Assess the safety and tolerability of M6620 (VX-970, berzosertib) when administered along with weekly cisplatin and radiation therapy (XRT) in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC). II. Establish the recommended phase 2 dose (RP2D) of the combination. SECONDARY OBJECTIVES: I. Characterize the pharmacokinetic (PK) profile of M6620 (VX-970, berzosertib). II. Assess for potential drug-drug interaction between M6620 (VX-970, berzosertib) and aprepitant. III. To observe and record anti-tumor activity. IV. To assess the rate of complete metabolic response (CMR) at 12 weeks post completion of chemoradiation using 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. V. To collect archival tumor material for retrospective analysis of association between tissue-based biomarkers and clinical outcome. OUTLINE: This is a dose-escalation study of berzosertib. Patients receive berzosertib intravenously (IV) over 60 minutes on day -7 and then weekly on day 2 and cisplatin IV over 30-60 minutes weekly on day 1. Patients also undergo radiation therapy once daily, 5 days a week. Treatment continues for up to 7 weeks in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT), PET/CT, or magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up for 30 days, every 2 weeks for 3 months, and then every 3 months for 2 years.