KEYNOTE-040: A phase III randomized trial of pembrolizumab (MK-3475) versus standard treatment in patients with recurrent or metastatic head and neck cancer.

Abstract

TPS6084 Background: Prognosis of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is poor, with limited treatment options and survival rates of 6-9 months following standard-of-care (SOC) therapies. Pembrolizumab, a humanized IgG4 monoclonal antibody against PD-1 designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2, has demonstrated clinical efficacy by investigator review (confirmed and unconfirmed responses) in a phase I study of R/M HNSCC. Preliminary PD-L1 biomarker data suggest that response rate may be greater in PD-L1–positive patients. Methods: In this global open-label, phase III KEYNOTE-040 (NCT02252042) trial, 466 subjects with recurrent or metastatic HNSCC that have failed prior platinum therapy will be randomized (1:1) to pembrolizumab (200 mg Q3W) vs investigator’s choice SOC (single-agent methotrexate, docetaxel, or cetuximab). Randomization will be stratified by ECOG PS (0 vs 1), human papillomavirus (HPV) status in oropharyngeal cancer by p16 immunohistochemistry testing (positive vs negative), and centralized PD-L1 status (positive vs negative). Pembrolizumab will be given for ≤ 24 months or until disease progression, unacceptable toxicity, or investigator decision. AEs will be assessed according to NCI CTCAE, v4.0. Imaging will occur per RECIST v1.1 at 9 weeks and every 6 weeks thereafter. Modified RECIST, which allows for continued treatment after initial radiographic progression until confirmation imaging ≥ 4 weeks, will be used to account for unique responses seen with pembrolizumab. Radiographic responses will be confirmed by independent central review by RECIST v1.1 and modified RECIST and analyzed in real time for verification of progressive disease by RECIST v1.1. Survival follow-up will occur every 12 weeks. Primary end points are progression free survival (PFS) and overall survival (OS); secondary end points include ORR, DOR and PFS, OS, and ORR in PD-L1+ patients. Treatment differences in PFS and OS will be assessed using stratified log-rank test; Hazard ratios with 95% confidence intervals will be estimated using stratified Cox proportional hazard models. Clinical trial information: NCT02252042.