Tislelizumab versus placebo combined with induction chemotherapy followed by concurrent chemoradiotherapy and adjuvant tislelizumab or placebo for locoregionally advanced nasopharyngeal carcinoma: Interim analysis of a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial.

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6001 Background: Patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) have a risk of disease relapse after induction chemotherapy (IC)-concurrent chemoradiotherapy (CCRT). Early phase trials indicated that tislelizumab (PD-1 inhibitor) plus IC followed by CCRT have the potential to deepen responses and extend survival in LANPC. Here, we report the interim results of a phase 3 trial to evaluate the efficacy and safety of tislelizumab plus IC, followed by CCRT and adjuvant tislelizumab therapy in LANPC. Methods: Patients with high-risk LANPC (stage III-IVa, AJCC 8th Staging System, excluding T3N0, and T3N1 with retropharyngeal lymph nodes +) were randomized (1:1) to receive 200 mg tislelizumab or placebo + gemcitabine and cisplatin (GP) every 3 weeks (Q3W) for 3 cycles, followed by CCRT and adjuvant tislelizumab or placebo Q3W for up to an additional 8 cycles. Stratification factors were center and disease stage (III or IVa). Dual primary endpoints were complete response rate (CRR) after induction therapy and progression-free survival (PFS) per RECIST 1.1 by investigator under blinded review. The planned interim analysis (IA) for evaluating the first primary endpoint, CRR, was scheduled at 4 weeks after the completion of induction therapy to test whether addition of tislelizumab to standard IC significantly improved CRR, with allocated alpha at 0.005. Results: Between June 2022, and May 2023, 450 patients were randomized to tislelizumab arm (n = 223) and placebo arm (n = 227). Baseline characteristics were balanced between the two arms. At IA, 93.7% and 93.8% of patients completed 3 cycles of induction therapy in tislelizumab arm and placebo arm, respectively. Significant improvement in CRR was observed in tislelizumab arm vs placebo arm in the intent-to-treat population (ITT) (30.5% vs 16.7%; P = 0.0006). Improvement in CRR in tislelizumab arm vs placebo arm was consistent across key subgroups including disease stage (III [33.8% vs 20.7%]; IVa [28.7% vs 14.5%]), sex (male [28.3 % vs 15.7%]; female [38.0% vs 19.7%]), and ECOG PS (PS of 0 [28.8% vs 16.2%]; PS of 1 [40.6% vs 19.4%]). The ORR was 93.3% in the tislelizumab arm and 90.7% in the placebo arm. In safety population (tislelizumab arm, n=219; placebo arm, n=224), the incidence of Grade ≥3 TEAEs (40.6% vs 39.3%) and SAEs (2.3% vs 1.3%) were similar between two arms. Conclusions: The trial met its first primary endpoint with a statistically significant improvement of CRR with the addition of tislelizumab to standard IC in high-risk LANPC. Induction therapy with tislelizumab plus GP was generally well tolerated with manageable safety profile. Continued follow-up is being conducted to assess long-term efficacy and safety. Clinical trial information: NCT05211232 .