67MO - Neoadjuvant and Adjuvant Toripalimab in High-risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomised, Double-blind, Placebo-controlled, Phase 2 Trial

Background

Patients (pts) with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) with high pretreatment plasma Epstein–Barr virus (EBV) DNA remain at high risk for recurrence after platinum-based concurrent chemoradiotherapy(CCRT). The purpose of this single-center, randomized, double-blind, phase 2 study is to compare the efficacy and safety of toripalimab (anti-PD-1) and CCRT versus placebo and CCRT in pts with high-risk LA-NPC.

Methods

Pts with initially diagnosed stage III- IVA nasopharyngeal carcinoma ( pretreatment plasma EBV DNA ≥1500 copies/ml) were randomized 2:1 to receive neoadjuvant toripalimab (240 mg) or placebo once every 2 weeks for 2 cycles, followed by CCRT and adjuvant toripalimab (240 mg) or placebo once every 3 weeks for up to 8 cycles. The primary endpoint was 2-year progression-free survival (PFS) rate according to the investigator’s assessment in the intention-to-treat (ITT) population. Secondary end points included overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), major pathological response (MPR) in nasopharynx biospy, overall response (ORR), quality-of-Life and safety.

Results

From December 2019 to December 2021, 150 pts were randomized to the neoadjuvant-adjuvant toripalimab group (n = 100) and the placebo group (n = 50). At a median follow-up of 26.9 months, a statistically significant improvement in 2-year PFS rate by the investigator’s assessment in the ITT population was demonstrated for the toripalimab group vs placebo group (91.8% vs 73.9%; HR = 0.33, 95% CI: 0.15 - 0.76, P =0.006). The 2-year OS rate was 100% and 94.0% (HR = 0.10, 95% CI: 0.01 - 0.82, P = 0.008), 2-year DMFS and LRFS were 92.8% vs 80.0% and 99.0% vs 82.0%, respectively. No new safety signals were identified, the incidence of grade≥3 treatment-related adverse events were similar between two groups (73.7% vs 68.0%).

Conclusions

The addition of neoadjuvant and adjuvant toripalimab to CCRT provided a significant improvement in 2-year PFS rate for the high-risk LA-NPC pts with an acceptable safety profile.

Clinical trial identification

NCT03925090.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.