Low-dose radiotherapy combined with neoadjuvant chemotherapy and an anti-PD-1/CTLA-4 bispecific antibody cardonilizumab for resectable locally advanced head and neck squamous cell carcinoma: Preliminary report of a single-arm, prospective phase II cl

e18026 Background: About 70% ~ 80% of head and Neck Squamous Cell Carcinoma (HNSCC) patients are locally advanced (stage III-IVB) at the time of initial diagnosis. As the current neoadjuvant chemotherapy unable to meet the requirements of pathological response and overall survival, some studies have used immune checkpoint inhibitors (ICIs) to increase pathological response. Our previous study has revealed that low-dose radiotherapy can improve the response of tumor to ICIs. Therefore, we conducted this clinical trial aimed at evaluating the efficacy and safety of low-dose radiotherapy combined with cardonilizumab, an anti-PD-1/CTLA-4 bispecific antibody and nab-paclitaxel plus cisplatin as neoadjuvant therapy for resectable HNSCC. Methods: This was a Phase II, open-label, single-arm study which registered in Chinese Clinical Trial Registry (ChiCTR2400084430). Newly diagnosed HNSCC patients with staging III-IVB were included. The neoadjuvant treatments were administered as follows: low-dose radiotherapy, (1Gy/1 fraction, D1, D2, D8, D15,Q3W), cardonilizumab (10mg/Kg, D1 Q3W) and nab-paclitaxel and cisplatin (90mg/m 2 and 20 mg/m 2 respectively, D1, D8, D15 Q3W) for two cycles. Radically surgical resection was administered 3-4 weeks after neoadjuvant treatments. The main objective of this trial was pathologic complete response (pCR). The secondary objectives included major pathological response (MPR) , objective Response Rate (ORR), adverse events, surgical delay rate, quality of life; R0 resection rate; 3-year progression-free survival (PFS) and overall survival (OS). Results: From May 20, 2024 to January 20, 2025, 10 patients have completed neoadjuvant therapy. 6 of them have received radical surgery, 2 patients (33.3%) achieved a pCR, 4 patients (66.7%) achieved MPR. The ORR was 100%. No surgery delay was observed. All the 6 patients achieved R0 resection. The other 3 out of the 10 patients have completed MRI evaluation 4 weeks after completing neoadjuvant therapy，2 of the 3 patients were scheduled for radical surgery and one refused surgery. The remaining 1 out of the 10 patients is scheduled for MRI follow-up after neoadjuvant therapy. Therefore, the 9 patients who have completed MRI examinations were assessed according RECIST criteria: 1/9 (11.1%) CR, 6/9(66.7%) PR, 2/9(22.2%) SD. The rate of grade 3 or 4 toxicities was 15.4% (2/13) and both are neutropenia. Conclusions: Low-dose radiotherapy combined with cardonilizumab and nab-paclitaxel plus cisplatin as neoadjuvant therapy for HNSCC has sufficient power to downsize tumors and provide outstanding tumors pathologic response and R0 resection, with acceptable safety and adverse effect. Next, further validation will carry out with larger sample size. Clinical trial information: ChiCTR2400084430 .