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.
