Ramucirumab and Pembrolizumab vs Pembrolizumab Monotherapy in PD-L1 Positive Head and Neck Squamous-Cell Carcinoma

Inclusion Criteria: * Incurable RM-HNSCC, defined as RM disease or second or subsequent primary HNSCC not amenable to cure by surgery and/or radiation therapy or patient declines or is ineligible for curative therapy. Eligible primary tumor sub-sites include oral cavity, oropharynx, larynx and hypopharynx only. * PD-L1 positive (CPS ≥1) disease, based on local IHC assay using 22C3 antibody. * Measurable disease per RECIST 1.1. * No prior systemic therapy for RM-HNSCC. RM disease developing within 6 months of completion of either a) systemic platinum or cetuximab therapy given as a component of a curative-intent multi-modality regimen or b) radiation therapy and/or surgery is eligible. * At least 18 years of age. * ECOG performance status 0-1. * Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1.5 K/cumm * Platelets ≥ 100 K/cumm * Hemoglobin ≥ 9.0 g/dL * Total bilirubin ≤ 1.5 x IULN * AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN. In the setting of liver metastases, AST(SGOT)/ALT(SGPT) ≤ 5.0 x IULN * Creatinine ≤ 1.5 x ULN. If patient has creatinine \> 1.5 x ULN, then 24 hour urine collection must be performed and creatinine clearance must be ≥ 40 mL/min by Cockcroft-Gault * Urine protein to creatinine ratio (UPC) ≤ 1; if UPC \> 1, then a 24-hour urine protein must be assessed and patient must have a 24-hour urine protein value \< 1 g to be eligible * INR ≤ 1.5 (≤ 3.0 if on warfarin) and PTT ≤ 1.5 x ULN (Patients are allowed to be on a…