A single-arm, open-label, multicenter, phase IIIb clinical trial with nivolumab in subjects with recurrent or metastatic platinum-refractory squamous cell carcinoma of the head and neck

Abstract

Abstract Background Nivolumab is an established treatment for recurrent/metastatic (RM) head and neck squamous cell carcinoma (HNSCC) patients (pts) failing platinum-based treatment. However, knowledge about safety and activity data are limited to pts enrolled into clinical trial leading to drug approval. Methods We conducted a single-arm, open-label, multicentre prospective phase IIIb clinical trial with nivolumab 240\xa0mg in subjects with RM HNSCC. Primary objective was to assess the incidence of high-grade (CTCAE v 4.03 grade 3 or higher), treatment-related (TR), selected adverse events (AE); secondary objectives were to characterize the outcome of all AE in terms of duration, time to event onset, and event resolution. Moreover, we assessed Overall Response Rate (ORR), OS and PFS and we analysed in an exploratory way clinical and biomolecular factors associated with improved outcome. A subgroup analysis was also performed in 20 pts to define baseline immunologic profiles and their changes along the treatment. Results We enrolled 127 pts with the following characteristics: male (82%), age higher than 65 years (43%), with primary cancer in oral cavity (33%), oropharynx (31%), larynx (24%), hypopharynx (8%) or other sites (4%). Performance status was 0 in 34% and 1 in 63% pts; 27% of the pts had received 2 or more systemic lines of therapy before. Grade 3-4 TR AE happened in 11% of the pts (anemia 2%, pneumonitis and encephalitis 1%), while all-grade TR AE were 40% (fatigue 20%, hypothyroidism 8%, anemia and pruritus 6%). Median duration of grade 3-4 TR AE was 10 days (4-22) and of grade 1-2 TR AE 63 days (1-336). Median OS and PFS were 7 months (5-NR) and 2 months (1.5-2.5) and ORR 12%. Pts experiencing any TR AE had an improved OS; HR 0.459 (0.254-0.827, p\xa0=\xa00.0096). Analyses of stromal tumor-infiltrating lymphocytes (TILs) status and PD-L1 status (clone 28-8 Agilent) are ongoing. Conclusions In this phase IIIb trial, nivolumab confirmed the safety and efficacy profile of the registration trial. Experiencing any grade TR AE revealed to be a favorable prognostic factor, as possible expression of effective immune response. Legal entity responsible for the study GONO group. Funding Bristol Myers-Squibb. Disclosure P. Bossi: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Angelini; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Voluntis. M.C. Merlano: Honoraria (self), consultancy or A.B.: Bristol M.S.; Honoraria (self), consultancy or A.B.: Merck S.D.; Honoraria (self), consultancy or A.B.: Merck; Shareholder / Stockholder / Stock options, Stocks: Glaxo SK; Research grant / Funding (institution), Support for clinical trials: Merck. M.G. Ghi: Honoraria (self), Advisory role: BMS; Honoraria (self), Advisory role: MSD; Honoraria (self), Advisory role: Merck Serono. G. Rinaldi: Honoraria (self), Research grant / Funding (self), Speaker and PI in clinical Trial: Novartis; Honoraria (self), Research grant / Funding (institution), Speaker and PI in clinical Trial: BMS; Research grant / Funding (self), PI in clinical Trial: MSD. F. Morelli: Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): BMS. A. Farnesi: Honoraria (self), speaker: Bayer; Honoraria (self), speaker: Novartis. D. Galizia: Honoraria (self), public speaker: BMS; Honoraria (self), congress travel costs coverage: Merck; Honoraria (self), congress travel costs coverage: Roche; Honoraria (self), congress travel costs coverage: Angelini. L.F. Licitra: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: BMS; Honoraria (self), Research grant / Funding (institution), Speaker: Eisai; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: MSD; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: Merck-Serono; Honoraria (self), Research grant / Funding (institution), Speaker: Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution), Speaker: Novartis; Honoraria (self), Research grant / Funding (institution), Speaker: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Speaker: Roche; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Bayer; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Debiopharm; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Sobi; Honoraria (self), For teaching in medical meetings: Incyte Biosciences Italy srl; Honoraria (self), Expert opinion in advisory board meetings: Doxa Pharma srl; Honoraria (self), For public speaking in medical meetings: Amgen; Honoraria (self), Expert opinion in advisory board meetings: Nanobiotics Sa; Honoraria (self), For public speaking in medical meetings and/or expert opinion in advisory boards: GSK; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2016-2017): Celgene International; Research grant / Funding (institution), Founds to my Institution for 2 clinical trials (2014-2018): Exelixis Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2014-2015): Hoffmann-La Roche Ltd.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2017): IRX Therapeutics, Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2016): Medpace Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2014): Pfizer; Travel / Accommodation / Expenses, Travel coverage for medical meetings: Stilema, AccMed, Aiocc, Aiom. All other authors have declared no conflicts of interest.