This study aims to investigate the efficacy and safety of combining sintilimab and the TP regimen with/without IBI110 for neoadjuvant chemotherapy in resectable locally advanced head and neck squamous cell carcinoma (HNSCC).
The NCCN guidelines recommend that for resectable locally advanced HNSCC, the recommended treatment include surgery combined with postoperative adjuvant radiotherapy (chemoradiotherapy), or concurrent chemoradiotherapy; for locally extensive HNSCC, the guidelines recommend considering neoadjuvant chemotherapy, with subsequent selection of surgery or chemoradiotherapy based on the efficacy of the neoadjuvant chemotherapy. In recent years, multiple studies have shown that combining PD-1 inhibitors with neoadjuvant chemotherapy may help improve the pathological response rate of surgical resection. LAG-3 (Lymphocyte Activation Gene 3) is a cell surface molecule co-expressed with CD4 and CD8 on activated CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells. LAG-3 is an activation-induced T cell receptor (TCR) co-receptor with high affinity for major histocompatibility complex (MHC) class II molecules, and it can directly inhibit TCR signal transduction in the immune response through its interaction with MHC II. IBI110 can directly bind to LAG-3 on T cells, blocking the interaction between LAG-3 and MHC II, thereby relieving the inhibitory effect of LAG-3 on T cell activation and enhancing the anti-tumor immune response of T cells. Additionally, LAG-3 and PD-1 are both immune checkpoint receptors. Co-inhibition of LAG-3 and PD-1 can enhance immune responses and inhibit tumor growth. Therefore, IBI110 and its combination therapy with PD-1 monoclonal antibodies have great development potential in the treatment of locally advanced, recurrent, and late-stage solid tumors. Based on the aforementioned foundation, this study intends to enroll patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC). The treatment protocol will involve neoadjuvant therapy and the TP regimen (paclitaxel and cisplatin), with/without IBI110 for neoadjuvant chemotherapy. Following neoadjuvant therapy, patients will undergo radical surgery, and adjuvant radiotherapy (chemoradiotherapy) will be administered postoperatively based on pathological risk factors as appropriate. The primary endpoints of the study are efficacy and safety.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITINGMajor pathological response
The major pathological response rate (MPR rate), defined as the presence of residual tumor components ≤10% in tumor bed of the primary tumor site and cervical lymph node.
Time frame: Up to 3 months, post-surgery
Adverse Events related to treatment
Adverse Events related to treatment of sintilimab, IBI110, paclitaxel and cisplatin, per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: Up to 4 months
Pathologic complete response rate
Pathologic complete response rate
Time frame: Up to 3 months, post-surgery
Objective response rate
Objective response rate of primary tumor and metastatic lymph nodes, per RECIST 1.1 criteria
Time frame: Up to 2 months, prior to surgery
Progression-free survival rate
Progression-free survival rate
Time frame: Up to 2 years
Overall survival rate
Overall survival rate
Time frame: Up to 2 years
Quality of life asessment
Quality of life evaluation, based on EORTC QLQ-H\&N35 criteria
Time frame: Up to 2 months, prior to surgery
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Chemotherapy
Definitive surgery
Adjuvant radiotherapy or chemoradiotherapy based on post-operative pathologic findings.