Phase III randomized trial of tislelizumab plus gemcitabine/capecitabine (GX) versus tislelizumab plus gemcitabine/cisplatin (GP) as first-line therapy for recurrent/metastatic nasopharyngeal carcinoma: A prospective multicenter study (PROGRESS).

Abstract

TPS6125 Background: Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China. Around 10% of pts have distant metastasis at initial diagnosis, and ~30% of those initially without metastasis will develop distant metastasis after radical treatment. These recurrent/metastatic (R/M) NPC pts have poor prognosis with a 5-year survival rate of only 20–30%. The RATIONALE-309 study established tislelizumab plus GP as a standard first-line therapy for R/M NPC, but most pts still experience disease progression in 2 years. Furthermore, in real-world clinical practice, a lot of pts are either platinum-intolerant or platinum-refractory recurrent, underscoring the urgent need for novel treatments. Recent studies suggest that first-line treatment regimens incorporating capecitabine may provide longer progression-free survival (PFS) compared to the GP regimen with a more favorable safety profile. Additionally, a retrospective study demonstrated that tislelizumab plus GX achieved notable tumor responses and PFS benefits in R/M NPC pts who have relapsed immunotherapy. Methods: This is a prospective, multicenter, randomized, controlled Phase III trial evaluating the efficacy and safety of tislelizumab + GX vs. tislelizumab + GP as first-line therapy in R/M NPC. 266 pts will be randomly assigned to the experimental or the control group. The experimental group will receive tislelizumab plus GX (gemcitabine 1g/m² D1,8 + capecitabine 1000 mg/m² BID D1-14) for 4–6 cycles, followed by tislelizumab plus capecitabine maintenance. The control group will receive tislelizumab plus GP (gemcitabine 1 g/m² D1,8 + cisplatin 80mg/m² D1) for 4–6 cycles, followed by tislelizumab monotherapy. Treatment will continue until disease progression or intolerable toxicity. The primary endpoint is PFS. Secondary endpoints include objective response rate, duration of response, overall survival, etc. Adverse events will be monitored and graded according to NCI CTCAE v5.0. Patient enrollment began in December 2023 across 10 centers in China, with 168 pts enrolled by December 2025. Clinical trial information: NCT06177301 .