Neoadjuvant Finotonlimab Plus TP Regimen in Locally Advanced INI-1-Deficient Sinonasal Carcinoma

This is a prospective, multicenter, single-arm phase 2 study in adults with locally advanced (T3/T4) INI-1 (SMARCB1)-deficient sinonasal carcinoma, a very rare and aggressive cancer of the nasal cavity and sinuses. This cancer often invades the skull base, eyes, nerves, and surrounding critical structures, making surgery difficult and potentially disabling. Current standard treatment is usually surgery followed by radiotherapy, but complete removal is often difficult and recurrence is common. Standard chemotherapy before surgery has shown limited tumor shrinkage, so better pre-surgical treatment is urgently needed. The purpose of this study is to find out whether giving an immunotherapy drug, finotonlimab, together with standard chemotherapy (paclitaxel plus cisplatin, the "TP" regimen) before surgery can shrink the tumor and improve treatment results. Finotonlimab is a PD-1 inhibitor that may help the immune system attack the cancer, and it is being given together with chemotherapy because the two treatments may work better in combination. All participants will receive 2 cycles of this combined treatment (each cycle is 21 days), followed by imaging tests to measure tumor response. If the tumor is considered removable, participants will then undergo surgery and, after recovery, standard postoperative radiotherapy. The main question this study is trying to answer is: how many participants experience significant tumor shrinkage (objective response, defined as complete or partial response) after 2 cycles of neoadjuvant finotonlimab plus TP chemotherapy, as assessed by blinded independent imaging review using RECIST v1.1. The study will also look at safety, the rate of complete surgical removal (R0 resection), pathological response, disease-free and overall survival, quality of life, and whether important organs such as the eye can be preserved. About 20 participants will be enrolled across multiple centers. This study is expected to provide the first prospective evidence for this combination in this rare cancer and may help establish a new treatment option before surgery.

Inclusion Criteria: 1. Age 18-75 years, male or female. 2. Complete loss of nuclear INI-1 (SMARCB1) expression in tumor cells confirmed by central pathology immunohistochemistry, with a pathological diagnosis of primary malignant tumor of the sinonasal cavity and skull base. 3. No prior radiotherapy of any type, including proton/heavy-ion radiotherapy or intensity-modulated radiotherapy. 4. AJCC 8th edition stage T3, T4a, or T4b; N0-N2 lymph node metastasis is allowed; isolated distant metastases assessed by MDT as stable and amenable to concurrent local treatment are allowed; extensive multiple distant metastases are excluded. 5. MDT assessment indicates extensive local invasion of the skull base and/or orbit, high difficulty for direct surgery, high risk of residual disease, and suitability for neoadjuvant downstaging. 6. ECOG performance status 0-1 and expected survival ≥6 months. 7. Baseline laboratory values meet treatment safety standards: absolute neutrophil count ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥90 g/L; ALT/AST ≤2.5 × ULN; total bilirubin ≤1.5 × ULN; serum creatinine ≤1.5 × ULN; creatinine clearance ≥60 mL/min; LVEF ≥50%; and no significant thyroid dysfunction. 8. Voluntary participation with full understanding of benefits and risks, and signing of two copies of the informed consent form. Exclusion Criteria: 1. Prior use of PD-1/PD-L1 inhibitors, taxane chemotherapy, or platinum-based chemotherapy. 2. History of severe allergy to finotonlimab, paclitaxel, cisplatin, or any of their excipients. 3. Active autoimmune disease, interstitial lung disease, active tuberculosis, or uncontrolled severe infection. 4. Severe cardiovascular or cerebrovascular disease, uncontrolled hypertension, or severe hepatic or renal failure. 5. History of another malignancy within 5 years, except adequately treated basal cell skin cancer or carcinoma in situ. 6. Pregnant or breastfeeding women. 7. Men or women of childbearing potential who are unwilling to use adequate contraception during treatment and for 6 months after the end of treatment. 8. Participation in another anticancer clinical trial within 30 days before enrollment. 9. Psychiatric disorders, poor compliance, or inability to complete follow-up. 10. Extensive multiple intracranial metastases or inability to tolerate systemic treatment.