Abstract CT131: NCI#9673 phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal: Immunologic correlates of response
Authors: Morris Van , Mahvash Armeen , Vence Luis , Blando Jorge , Wolff Robert A. , Ohinata Aki , Ohaji Chimela , Allison James , Sharma Padmanee , Eng Cathy 
Published: July 2016

Abstract
Introduction: The incidence of squamous cell carcinoma of the anal canal (SCCA) continues to increase, with no standardized treatment options for patients with refractory metastatic disease. The development of SCCA is associated with human papillomavirus infection (HPV) and impaired immunity. Nivolumab is a monoclonal antibody targeting the programmed-death 1 (PD-1) ligand on T cells and may restore T-cell activity against tumor cells. The efficacy for nivolumab for metastatic SCCA has not been evaluated. Methods: Patients with at least one prior treatment for metastatic SCCA were treated with nivolumab (3 mg/kg) intravenously every 2 weeks in this single-arm, Simon two-stage phase 2 trial. PD-L1 expression was not an inclusion criterion. A total of 39 patients were enrolled through the ETCTN network. At our institution, an exploratory correlative analysis of paired tumor biopsies (pre-treatment and on-treatment) and of serial peripheral blood samples was conducted. All tissues samples were analyzed by immunohistochemistry (IHC) and flow cytometry by the MDACC immunotherapy platform to identify various immune cell subsets. Results from radiographic responders and non-responders were compared by Mann-Whitney test to identify biomarkers associated with treatment response. Results: In this subset analysis, 17 patients consented to tissue collection. Four patients had inadequate sample for analysis. Immune monitoring studies of pre-treatment tumor samples by IHC (n = 13) revealed a significantly higher percentage of CD3 T cells (p = 0.02), CD8 T cells (p = 0.01), granzyme-B (p = 0.005), PD-1 (p = 0.02), and PD-L1 on tumor epithelial cells (p = 0.005) in samples from patients who were scored as responders (n = 4) as compared to non-responders (n = 9). Five additional markers (CD20, CD45R0, CD68, FoxP3, OX40) measured by IHC did not show statistically significant differences. In addition, flow cytometry studies on available tumor samples (n = 12) indicated that patients who scored as responders had a significantly higher frequency of TIM-3+ CD8 T cells (p = 0.003) and PD-L1+ CD45+ immune cells (p = 0.03) in pre-treatment samples. Of note, responder patients had a trend towards a decrease in frequency of TIM-3+ CD8 T cells in post-treatment tumor samples. Conclusions: In the first prospective phase II trial ever for refractory metastatic SCCA, our exploratory analysis of pre- and on-treatment tissue specimens revealed potential correlations between immunologic biomarkers and clinical outcomes to nivolumab. Additional immune monitoring data will be provided.
Citation Format: Van Morris, Armeen Mahvash, Luis Vence, Jorge Blando, Robert A. Wolff, Aki Ohinata, Chimela Ohaji, James Allison, Padmanee Sharma, Cathy Eng. NCI#9673 phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal: Immunologic correlates of response. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT131.