Most patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. While cisplatin-based chemoradiotherapy remains the standard-of-care treatment for this patient population, it is still associated with a high rate of disease recurrence. Given the relatively high mutational burden of HNSCC, immunotherapy has emerged as a promising therapeutic strategy. The addition of PD-1 inhibitors to induction chemotherapy has been shown to improve antitumor responses without increasing treatment-related toxicity. In addition, radiotherapy can further potentiate systemic antitumor immune responses.
Sintilimab, a PD-1 monoclonal antibody, has demonstrated robust antitumor activity across multiple solid malignancies. Early clinical evidence indicates a synergistic antitumor effect when combined with hypofractionated radiotherapy. Nevertheless, clinical data regarding the combination of sintilimab with chemoradiotherapy in locally advanced HNSCC remain limited.
Accordingly, we designed a multicenter, single-arm phase II trial to evaluate the efficacy and safety of sintilimab in combination with definitive chemoradiotherapy for patients with locally advanced HNSCC.
1. Provide written informed consent and understand and agree to comply with study requirements and the study visit schedule.
Hematology: Absolute neutrophil count (ANC) ≥1.5×10⁹/L or within normal range; Platelet count (PLT) ≥100×10⁹/L; Hemoglobin (HGB) ≥90 g/L.
Hepatic function: Total bilirubin (TBIL) ≤1.5×ULN; For subjects with Gilbert's syndrome, TBIL ≤3×ULN; For subjects without liver metastasis, AST and ALT ≤2.5×ULN; For subjects with liver metastasis, AST and ALT ≤5×ULN; Albumin (ALB) ≥28 g/L.
Renal function: Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance rate (CCR) ≥60 mL/min (calculated by Cockcroft Gault formula or measured via 24 hour urine collection); Urinalysis showing urinary protein <2+. Subjects with baseline urinary protein ≥2+ must undergo 24 hour urine collection with 24 hour urinary protein <1 g (if both assays are performed, the 24 hour urine result will be used for eligibility determination).
1. History of hypersensitivity to PD 1 agents or platinum containing components.
Previous treatment with anti PD 1, anti PD L1, or anti CTLA 4 antibodies.
Use of any investigational drug within 4 weeks prior to the first dose of study drug.
Concurrent participation in another clinical trial, unless it is an observational (non interventional) clinical study.
Single group
Hypofractionated Induction RT (5Gy×3) Followed by Sintilimab, Platinum-Based CCRT and Sintilimab
Combination productInduction therapy consists of two cycles of sintilimab injection combined with hypofractionated radiotherapy (5 Gy × 3), followed by sequential concurrent chemoradiotherapy delivered at 50 Gy in 25 fractions with two cycles of platinum-based chemotherapy (cisplatin, nedaplatin or carboplatin). Upon completion of chemoradiotherapy, patients are administered maintenance sintilimab injection for a minimum of six months.
1-year progression-free survival rate (1-year PFS rate)
The proportion of patients who remain alive without disease progression (including local recurrence, regional recurrence, distant metastasis, or death) one year after the start of treatment.
Objective Response Rate (ORR)
Objective Response Rate (ORR) refers to the proportion of patients who achieve a measurable reduction in tumor burden, specifically those who experience a complete response (CR) or partial response (PR) according to standardized criteria (such as RECIST).
Progression-free survival(PFS)
Progression-free survival is the length of time from the start of treatment (or from randomization/enrollment) until the disease progresses or the patient dies from any cause, whichever occurs first.
Distant Metastasis-Free Survival (DMFS)
Distant Metastasis-Free Survival (DMFS) is the length of time from the start of treatment (or from diagnosis/enrollment) until the first occurrence of distant metastasis or death from any cause, whichever happens first.
Overall Survival(OS)
Overall Survival(OS) is defined as the period from the date of first treatment administration to the date of death due to any cause.
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