Safety and disease control achieved with the addition of nivolumab (Nivo) to chemoradiotherapy (CRT) for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG Foundation 3504

6073 Background: Nivo, which inhibits the programmed death-1 (PD-1) receptor, improved survival for pts with platinum-refractory recurrent/metastatic HNSCC. A clinical trial evaluated the safety of adding nivo to 4 standard intensity modulated (chemo) radiotherapy (RT) regimens (see table) for pts with newly diagnosed IR/HR HNSCC. Primary endpoint was safety and feasibility. Methods: Eligibility included IR (p16+ oropharynx [op], T1-2N2b-N3/T3-4N0-3, >10 pack-years [pys], or T4N0-N3/T1-3N3, ≤10 pys) & HR HNSCC (oral cavity, larynx, hypopharynx, p16- op, T1-2N2a-N3/T3-4N0-3). 10 pts/arm (8 evaluable; 0-2/8 DLTs acceptable). Nivo (dose & schedule varied per arm) started 2 wks pre-RT & continued 3 months post-RT. Feasibility of adjuvant nivo months 3-12 post-RT defined as ≥4 of 8 pts/arm received 7 doses. Arm 4 limited to age ≥70, Zubrod performance status (PS) 2, CrCl 10 pys, 62% p16+ op, 72% T3-4, 85% N2-3. Grade ≥3 nivo-related AEs: adrenal insufficiency, diarrhea-3, anemia, fatigue-2, mucositis-3, nausea, vomiting, lipase increase-6, amylase increase-2, lymphocyte/neutrophil/WBC decrease-4, hyponatremia-3, anorexia, maculo-papular rash. SAE in 4/10, 4/9, 5/10 & 4/10. DLTs, adjuvant chemo feasibility, median follow-up (mo), progression or death events per arm shown in table. Conclusions: Nivo concomitant with all (chemo)RT regimens was safe for patients with newly diagnosed IR/HR HNSCC but adjuvant nivo was infeasible after high-dose cisplatin or in cisplatin-ineligible patients ( NCT02764593 ). Preliminary data on progression/death is provided. Acknowledgements: Support for this study was provided by Bristol-Myers Squibb Company. Clinical trial information: NCT02764593. [Table: see text]