Immunotherapy with pembrolizumab in surgically resectable head and neck squamous cell carcinoma.

TPS6110 Background: Patients with locally advanced, surgically resectable Stage III/IV human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) suffer from locoregional and distant metastatic (LRR/DM) failures. This population is thus an ideal target for checkpoint blockade therapy as the mutational landscape of these carcinogen-induced malignancies bears a rich array of antigenic targets for immune based therapeutics. Methods: Trial design and statistical methods This is a Phase II neoadjuvant and post-operative pembrolizumab trial. After informed consent and registration, tumor biopsy and peripheral blood will be obtained and patients will receive a single pre-operative dose of pembrolizumab (10 mg/kg). After two to three weeks, patients undergo definitive surgery where tissue is again harvested. Patients then proceed with standard post-operative adjuvant therapy dictated by the pathologic report. High-risk patients with extracapsular extension and/or positive margins receive additional maintenance pembrolizumab for the first year after treatment. Sample size justification: Historical data has shown a 35% rate of LRR and DM at 1 year in HNSCC patients undergoing multimodality treatment and our primary endpoint is to reduce LRR/DM to 15%. We will recruit 46 patients with 31 of these expected to be high risk and qualify for post-operative pembrolizumab. This cohort will allow us to detect with 80% power (alpha = 0.05) a difference of at least 20% in the 1-year LRR/DM rate. Correlative studies: Clinical outcomes will be correlated with tumor PD-L1 expression, neoantigen burden as defined by tumor exome sequencing and RNA-Seq in matched pre-and post-pembrolizumab treated samples. Finally, patient specific tumor infiltrating lymphocyte cultures will be used to define antigen-specific T cells targeted by pembrolizumab. Major eligibility criteria Patients must have stage III/IV HPV-negative HNSCC with planned primary surgical management. Current enrollment 10 of 46 patients enrolled Trial registry number NCT02296684 Clinical trial information: NCT02296684.