Concurrent cetuximab (CTX) and nivolumab (NIVO) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Safety results of a phase I/II study

6515 Background: While anti-Programmed Death-1 (anti-PD-1) inhibitors have efficacy, only some patients (pts) with R/M HNSCC achieve clinically significant benefits. We designed the study to determine the 1-year overall survival (OS) rate of concurrent CTX and NIVO in patients who had progressed on at least one prior treatment for their R/M HNSCC. Methods: Pts were treated with CTX 500 mg/m2 IV on Day (D) -14 as a lead-in followed by CTX 500 mg/m2 IV and NIVO 240 mg/m2 IV on D1 and D15 every 28-D cycle (C). Pts with CTX infusion reaction or who did not receive C1D1 for any reason were non-evaluable and replaced. NIVO dose reduction was not allowed but withheld/discontinued based on adverse event (AE) severity. Results: Total 47 pts are enrolled. 2 pts are non-evaluable. 45 evaluable pts are analyzed. Median age is 64 (24-77). ECOG performance status at baseline is 0 (9, 20%), 1 (33, 73%), and 2 (3, 7%). Primary sites are oral cavity 10 (22%), oropharynx 24 (53%), hypopharynx 3 (7%), larynx 6 (13%), and unknown primary 2 (4%). p16 status is available in 33 (73%). Prior treatments before the study enrollment are: chemotherapy (CT) 42 (93%), no CT 3 (7%), radiotherapy (RT) 38 (84%), no RT 7 (16%), checkpoint inhibitors (CPI) 23 (51%), and no CPI 22 (49%). PD-L1 combined positive scores (CPS) is available in 30 (67%). Median follow up time for overall survival (OS) is 12.6 months. The most common grade 3 treatment-related AE (TRAE) occurring ≥2 are fatigue 6 (13%) and rash-acneiform 2 (4.4%). The only grade 4 TRAE is CTX infusion reaction in 1 (2.2%). The most common grade 3 immune-related AE (IRAE) occurring ≥2 is fatigue 3 (6.7%). No grade 4 IRAE is observed. The median progression-free survival (PFS) and median OS are summarized in Table. Pts with no prior exposure to CPI have favorable PFS and OS relative to pts with prior CPI (PFS: HR 0.49, 95% CI 0.25-0.97, p=0.04 and OS: HR 0.5, 95% CI 0.22-1.14, p=0.09). Conclusions: Our data suggest the combination of CTX and NIVO is active in pts without prior CPI exposure and overall well tolerated in all pts. These preliminary results support further evaluation of the combination in CPI naïve pts. Clinical trial information: NCT03370276 . [Table: see text]