3652 - Phase II Trial of Tislelizumab plus Chemotherapy with Response-Adapted Radiotherapy for De Novo Metastatic Nasopharyngeal Carcinoma

Purpose/Objective(s):

De novo metastatic nasopharyngeal carcinoma (dmNPC) remains associated with a poor prognosis, despite the establishment of gemcitabine plus cisplatin combined with anti-PD-1 antibody as the current standard of care. Evidence from Phase III clinical trials has demonstrated that the addition of locoregional radiotherapy to chemotherapy can improve patient outcomes. However, preclinical studies have revealed that extensive irradiation of cervical lymph node drainage regions may attenuate the synergistic effect of immunotherapy. Therefore, this phase II study was designed to evaluate the efficacy and safety of tislelizumab (anti-PD-1 antibody) in combination with chemotherapy and response-adapted radiotherapy in patients with dmNPC.

Materials/Methods:

This is a single-center, single-arm, Phase II clinical trial. Patients with previously untreated dmNPC are eligible. All patients will receive induction therapy consisting of gemcitabine plus cisplatin combined with tislelizumab every 3 weeks for 4–6 cycles. Response-adapted radiotherapy will be delivered based on post-induction treatment response, as follows: Patients achieving complete response (CR) after induction therapy will not receive radiotherapy; For patients achieving partial response (PR), radiotherapy (55 Gy in 20 fractions, 5 fractions per week over 4 weeks) will be delivered to the residual primary nasopharyngeal lesion and metastatic cervical lymph nodes, with no prophylactic neck irradiation required. For metastatic lesions, radiotherapy will be administered either concurrently or sequentially with locoregional radiotherapy: stereotactic body radiation therapy (SBRT) will be prioritized, while conventional radiotherapy will be used for lesions unsuitable for SBRT. Tislelizumab administration will not be interrupted by radiotherapy and will continue until disease progression, development of unacceptable toxicity, or completion of a maximum treatment duration of 2 years. Tislelizumab will be administered without interruption by radiotherapy and will continue until disease progression, unacceptable toxicity, or a maximum treatment duration of 2 years. The primary endpoint is 1-year progression-free survival (PFS). Secondary endpoints include 1-year overall survival (OS), locoregional control, distant metastasis control, objective response rate (ORR), and duration of response (DoR). As of February 14, 2026, 9.4% of the planned 32 subjects have been enrolled. ClinicalTrials.gov Identifier: NCT07248696.

Results:

Clinical trial in progress.

Conclusion:

Clinical trial in progress.