Nivolumab (N) is the standard of care in pts with platinum refractory R/M HNSCC. Novel patterns of response and progression to immunotherapy (hyperprogression (HP), pseudoprogression (PSPD), dissociated responses (DR)) have been described that are not observed with conventional cytotoxic or targeted anticancer drugs. No prospective data have been reported for pts with R/M HNSCC. T was a single-arm, phase II trial that included, from 08/2017 to 11/2018, 343 pts with platinum refractory R/M HNSCC treated with N (3 mg/kg, Q2W) (Even et al Ann Oncol 2020). Timing of studied CT scans for this study was: pre-baseline, baseline before N, 1st evaluation (E1) at week 8, 2nd evaluation (E2) at week 16. Tumor response was evaluated by RECIST 1.1. HP was evaluated using the 3 first CT by 2 different methods (Champiat et al Clin Cancer Res 2017 (C), Ferrara et al JAMA Oncol 2018 (F)). PSPD was defined as progression at E1 and stabilization of tumor growth or response at E2. DR was studied at E1 and defined as objective response (OR) in loco-regional (LR) site and no OR in metastatic (M) site or no OR in LR site and OR in M site. Of the 115 pts evaluable with C method and the 118 with F method, 15 (13%, 95% confidence interval (CI) 7-21) and 9 (8%, 95%CI 4-14) respectively experienced HP. Of the 128 pts evaluable for PSPD, 4 (3%, 95%CI 1-8) met the criteria. 208 pts had CT at baseline and at E1: -144 pts had HN disease, OR in HN sites was observed in 9 pts (6%, 95%CI 3-12) -122 pts had M disease, OR in M sites was observed in 16 pts (13%, 95%CI 8-20) DR was evaluated in 58 pts who had disease in both LR and M sites: -No OR in LR site and OR in M site: 8 (14%) pts -OR in LR site and no OR in M site: 2 (3%) pts -No OR in LR and M sites: 48 (83%) pts -OR in LR and M sites: 0 (0%) pt Overall, the DR rate was 17% (95%CI 9-29). The rate of DR was 22% (10 pts) (95%CI 11-36) in the 46 pts who previously received HN radiotherapy (RT), and 0% (95%CI 0-26) in the 12 pts without prior HN RT. In this prospective study, we estimated the rate of R/M HNSCC pts with HP under N between 4 and 21%. The rate of PSPD is very low, which should be considered in our clinical practice. 17% (95%CI 9-29) of the pts presented DR, mainly by absence of OR in LR site while OR occurred in M site.