Four cycles of tislelizumab plus GP regimen as neoadjuvant therapy for high-risk (T4/N3) locally advanced nasopharyngeal carcinoma.

6089 Background: The efficacy of standard chemoradiotherapy for locally advanced nasopharyngeal carcinoma (LANPC) is still unmet need, especially for stage Ⅳa(T4/N3, AJCC 8th) NPC. The efficacy and safety of the 4 cycles neoadjuvant chemotherapy strategy in stage N2-3 LANPC has been confirmed. Meanwhile, immunotherapy has showed favorable tumor response and survival benefit for patients with LANPC. Therefore, this study investigated the efficacy and safety of four cycles tislelizumab plus GP regimen as neoadjuvant therapy for high-risk LANPC. Methods: Patients with stage IVa (T4/N3, AJCC 8th) NPC were enrolled and treated with neoadjuvant therapy (gemcitabine, 1000 mg/m 2 , on days 1 and 8, cisplatin, 80 mg/m 2 , on day 1, tislelizumab 200mg, on day 1) every 3 weeks for 4 cycles followed by standard concurrent chemoradiotherapy. The primary endpoint was complete response (CR) rate after neoadjuvant therapy. Secondary endpoints included overall response rate (ORR) after neoadjuvant therapy, disease-free survival, overall survival, and tolerance. Results: From February 2022 to June 2022, 25 patients were enrolled and 24 evaluable patients (median age 49 years old; 15 men [62.5%]) completed protocol-specified 4 cycles neoadjuvant therapy without delaying radiotherapy. 1 patient was withdrawn from the trial due to treatment of acute viral parotitis. The CR rate was 50% (12/24), achieving the predefined endpoint. The ORR of all evaluable patients was 91.7%. By the cut-off date of Jan 15 th 2026, the median follow-up time was 44.8 months. The median disease-free survival was not reached and 36-month disease-free survival was 91.7%(95% CI 70.6%–97.8%). Two patients died of diseases not related to nasopharyngeal carcinoma and treatment, while the other patients still have no disease progression. 13 (52%) of 25 patients had grade 3-4 acute treatment-related adverse events (TRAE). Grade 1-2 immune-related adverse events (irAE) was recorded in 18 patients (72%). No grade 3-4 irAEs occurred. 3 (12%) of 25 patients had long-term TRAEs. Conclusions: Four cycles of tislelizumab plus GP regimen as neoadjuvant therapy demonstrated promising tumor response, long-term survival benefit and manageable safety profile in high-risk LANPC patients. Clinical trial information: ChiCTR2200056941.