Preliminary efficacy and safety of camrelizumab combined with cetuximab and chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): A phase II clinical trial.

e18011 Background: Cetuximab and PD-1 inhibitors are widely used first-line therapy for R/M HNSCC and may provide potential synergy in R/M HNSCC. We conducted an open-label, single-arm, Simon's two-stage, phase II study of camrelizumab with cetuximab and cisplatin-based chemotherapy as first-line treatment in R/M HNSCC (NCT05673577). We report the results of stage 1 of this study. Methods: Eligible patients with R/M HNSCC not amenable to curative treatment were enrolled. Patients were treated with camrelizumab 200mg intravenously Q3W, cetuximab 400mg/m 2 loading dose followed by 250mg/m 2 weekly (21-day cycle), cisplatin 75mg/m 2 Q3W, for up to 6 cycles, and nab-paclitaxel 125mg/m 2 on d1, d8 (21-day cycle), for up to 6 cycles. Maintenance therapy with camrelizumab 200mg intravenously Q2W, cetuximab 500mg/m 2 Q2W were given until intolerable toxicity or disease progression. Simon-minimax design was applied, if 9 of the 21 patients achieve PR or CR in the first stage, another 19 patients will be included. The primary endpoint is ORR. Secondary endpoints include PFS, OS, safety, etc, andmolecular biomarkers will be tested as exploratory endpoints. Results: A total of 21 patients were enrolled in the stage 1, with a median age of 65y (range 34-72y), M:F 19:2,ECOG (0:1) 1:20, and primary sites of oral cavity (n=6), oropharynx (n=3), hypopharynx (n=2), larynx (n=8), and unknown (n=2). By the cutoff date of Jan 10 2024, 20 patients were followed up (1 withdrew because of refusing and discontinuing treatment after SD). In total, 2 (9.5%) CR, 18 (85.7%) PR and 1 (4.8%) SD were observed as best response for an ORR of 95.2% and a DCR of 100%, meeting pre-planned criteria for trial continuation. Meanwhile, 18 patients achieved PR and 1 patient achieved SD after receiving the first two cycles of treatment (2 patients didn't complete accurate radiologic assessment of tumor response after 2 cycles of treatment and were confirmed PR after 4 cycles). Out of 21, 13 patients completed planned cycles of treatment and started maintenance therapy, 5 patients were still under planned cycles. The only one case of progressive disease occurred during the maintenance period. Grade 3 or above treatment-related adverse events were observed in 47.6% patients. One patient discontinued camrelizumab due to pneumonia, and one patient discontinued cetuximab due to grade 3 rash. Three patients reported fatal AEs, which was caused by tumor hemorrhage in the re-irradiated site, severe infectious pneumonia and choking due to swallowing, respectively. Conclusions: Camrelizumab combined with cetuximab and cisplatin-based chemotherapy induced a high ORR with prompt tumor shrinkage and was well tolerated in the scenario of first-line R/M HNSCC. These results meet protocol specifications for trial continuation. Final results will include long-term and stage 2 results. Clinical trial information: NCT05673577 .