A pilot phase II trial of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin (NeoCPC) for locoregionally advanced, resectable squamous cell carcinoma of the head and neck.

6069 Background: For resectable squamous cell carcinoma of the head and neck (HNSCC), novel therapeutic approaches are still needed to improve outcomes. Neoadjuvant immunochemotherapy (NICT) is considered as a potentially effective strategy. We therefore conducted a pilot phase II trial to explore the efficacy and safety of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin (NeoCPC) in patients with locoregionally advanced, resectable HNSCC. Methods: In this open-label phase II trial, patients with untreated locoregionally advanced, resectable HNSCC (T2‒T4, N0‒N3b, M0; AJCC, 8th Edition) received NICT with camrelizumab (200 mg), nab-paclitaxel (260 mg/m 2 ) and cisplatin (60 mg/m 2 ) on day 1 of each 21-day cycle for three cycles, followed by radiotherapy or surgery. The primary endpoint was objective response rate (ORR) per RECIST version 1.1. Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), safety, disease-free survival (DFS), and overall survival (OS). Genomic biomarkers (genetic mutations, tumour mutational burden [TMB] and immune microenvironment) in baseline tumor samples were explored. Results: Between April 2021 and January 2022, 48 patients were enrolled (median age, 59 years [range 27–73]; 42 men [87.5%]). After completion of neoadjuvant therapy, patients underwent surgery (27, 56.3%), chemoradiotherapy (15, 31.2%), radiotherapy (five, 10.4%) or continued immunochemotherapy as maintenance therapy (one, 2.1%). At a median follow-up time of 415 days, the ORR was 89.6% (43/45). Of the 27 patients who had surgery, 17 (63.0%) patients had an MPR, including 15 (55.6%) with a pCR. Patients with ORR were more likely to achieve pCR. One patient died of lung metastasis 6 months after completion of treatment. The 1-year OS and DFS rates were both 97.9%. Only 3 (6.3%) patients had grade 3 treatment-related adverse events (AEs): one with pneumonitis and two with neurotoxicity. No unexpected immune-related AEs were observed. For genetic analysis, the most frequently mutated genes were TP53 (77.1%), CDKN2A, FAT1, CCND1 and NOTCH1. The lower radiographic tumor regression percentage was observed in TP53-altered ( p= 0.01) and TERT-altered ( p= 0.002) patients, whereas higher percentage was observed in HPV-positive patients. The median TMB was 3.15 mutations/MB. No significant difference was observed in TMB between patients with ORR and non-ORR (stable disease). There was a significant correlation between density of M1-like macrophage cells, CD8+ T cells in tumor area and radiographic tumor regression percentage ( p= 0.009, p= 0.0005, respectively). Conclusions: NeoCPC showed promising efficacy with a high ORR and pathologic response rate for locoregionally advanced, resectable HNSCC, with an acceptable safety profile. Clinical trial information: NCT04826679 .