Sintilimab Combined With Hypofractionated Radiotherapy Followed by Chemoradiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma: A Multicenter, Single-Arm, Phase II Clinical Study
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.
• 2\. Male or female subjects aged ≥18 and ≤75 years at the time of signing the informed consent form.
• 3\. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
• 4\. Histologically or cytologically confirmed stage III IVB head and neck squamous cell carcinoma as assessed by the investigator.
• 5\. No prior systemic therapy for head and neck squamous cell carcinoma (including chemotherapy, EGFR monoclonal antibodies, anti PD 1 or anti PD L1 antibodies, anti CTLA 4 antibodies and other immune checkpoint inhibitors).
• 6\. At least one measurable target lesion per RECIST version 1.1 criteria. 7. Expected survival time ≥12 weeks. 8. Adequate bone marrow and organ function (no administration of any cellular/blood components, colony stimulating factors or cytokines within 14 days prior to laboratory testing):
⁃ 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).
⁃ Coagulation function: International normalized ratio (INR) ≤1.5; Activated partial thromboplastin time (APTT) ≤1.5×ULN.
‣ 9\. Male and female subjects of non childbearing potential, or those who agree to use at least one highly effective contraceptive method during the study (starting 14 days prior to screening or first study drug administration, whichever occurs earlier, continuing for 180 days after the last dose of study drug).