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Objective Salivary gland cancers (SGC) are rare cancers with currently no standard treatment for recurrent/metastatic disease. Based on checkpoint inhibitors benefit in a broad range of tumours, NIvolumab in Salivary gland CArcinoma of the Head and Neck (NISCAHN) evaluated nivolumab efficacy in SGC.Methods and analysis In this phase II single-stage Fleming design, patients with SGC with a progressive disease progression within 6 months prior to entering the study, were divided into ACC (adenoid cytic carcinoma) and non-ACC. All received nivolumab for a maximum of 12 months. The primary endpoint was the non-progression rate at 6 months (NPR6m) according to Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), tumour growth rate, safety and quality of life (health-related quality of life).Results 46 patients with ACC and 52 patients without ACC were enrolled over 1 year. Median follow-up was respectively 29.2 months and 16.9 months for patients with ACC and non-ACC. In the ACC cohort, with 15/45 patients non-progressive at 6 months, the primary endpoint was met (33.3%; 95% CI 21.8 to NE). Nivolumab failed to demonstrate efficacy in the non-ACC cohort (NPR6m: 14.0%; 7/50 patients). ORR, PFS and OS were 8.7% (95% CI 2.4 to 20.8), 5.3 (95% CI 3.2 to 5.6) and 17.2 months (95% CI 12.5-NE) in the ACC cohort, and 3.8% (95% CI 0.5 to 13.2), 1.8 (95% CI 1.7 to 3.5) and 11.5 months (95% CI 7.5 to 14.8) in the non-ACC cohort. Nivolumab safety profile was consistent with previous reports.Conclusion Nivolumab has limited efficacy in SGC. Differential results were observed in the two cohorts. The primary endpoint was met in the ACC cohort and no new safety signals were identified.Trial registration number EudraCT number: 2016-001794-32/NCT03132038.

Background Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets.Methods We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort.Results Unsupervised clustering identified two “TME subtypes”, in each of the cohorts: the “immune-enriched” and the “immune-low”. Within AXIPAP trial cohort, the “immune-enriched” cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the “immune-enriched” group (adjusted p