Predictive biomarkers for response to nivolumab in head and neck squamous cell carcinoma (HNSCC) (NCT#03652142).

Abstract

6060 Background: Tumor immune cell compositions determine response to immunotherapy. For a better understanding of the mechanisms of resistance to nivolumab in HNSCC, we sought to investigate a prospective cohort of longitudinal HNSCC samples from recurrent/metastatic HNSCC pts treated with nivolumab and identify biomarkers of response and resistance. We will specifically focus on modulation of immune markers following two cycles of nivolumab. Methods: Patients with platinum-refractory HNSCC with no contraindication to nivolumab therapy are included in this study. Tumor biopsies are performed at baseline, 24-72 hours after the second cycle and at progression with appropriate written informed consent. Samples were assessed for the presence of Tertiary Lymphoid Structures (TLS), PD-L1 expression (TPS and CPS) and CD8 T cell infiltrates combined with Ki67 (CD8/Ki67 double IHC stain). The primary outcome measure of the study is change in the percentage of immune cells in post treatment compared to baseline biopsies. Secondary endpoints include safety of performing a second biopsy, best overall response rate, biomarker expression in association with response and survival. Evaluation of other biomarkers including tumor mutational burden, HLA class I and II expression and adaptive immunity cell populations using multiplex IF is ongoing. Results: Of 20 patients evaluable for response, 14 had PD (8 of whom showed hyper-progression) and 6 attained disease control (1 with PR). PD-L1 status (CPS or TPS) was not altered by treatment (p = 0.905) and CPS > 20 pre-treatment showed a favorable trend towards response (p = 0.117). Absence of tertiary lymphoid structures was associated with disease progression (p = 0.0374). Infiltrating plasma cell count remained unchanged pre- and post-treatment and was unrelated to response (p = 0.458). The percentage of proliferating CD8+ T cells (CD8+/Ki67+) increased in post-treatment biopsies in the entire population (p = 0.022) and especially in progressors (p = 0.039). Pre-treatment CD8+ T cell density was higher in patients with hyper-progression compared to progressors (p = 0.029). Conclusions: Increased percentage of proliferating CD8+ T cells in progressors might represent dysfunctional T cells as has been recently shown in melanoma pts (Li H et al Cell 2019) and clinical efforts to reactivate intratumoral T cells may augment the efficacy of PD1 checkpoint inhibitors. Clinical trial information: NCT03652142.