NCT06712888

Toripalimab vs. Placebo Wtih GP Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

Toripalimab Versus Placebo Combined With Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: a Multicenter, Randomized, Placebo-controlled, Double-blind, Phase 3 Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 466 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The main questions it aims to answer are: 1. Does the combination of GP induction chemotherapy and toripalimab improve the 3-year progression-free survival (PFS) compared to GP induction chemotherapy with placebo? 2. What are the differences in CR after induction therapy, 3-year overall survival (OS), locoregional progression, and distant progression between the two groups? 3. What are the differences in safety between the two groups? 4. Are there predictive biomarkers of therapeutic efficacy, such as changes in EBV DNA or immune parameters, that correlate with treatment outcomes? Researchers will compare the GP + toripalimab group with the GP + placebo group to see if the toripalimab combination shows superior efficacy. Participants will: Receive either GP chemotherapy with toripalimab or GP chemotherapy with placebo as induction therapy. Undergo concurrent chemoradiotherapy ± adjuvant metronomic capecitabine following induction therapy. Be monitored closely for safety and efficacy outcomes.

Detailed description

Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Gemcitabine plus cisplatin (GP) has been demonstrated an effective chemotherapy regimen for NPC patients in previous studies. The results of GP combined with concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma showed 10% of locoregionally advanced NPC patients had complete response after three cycles of GP induction chemotherapy, and GP induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival (85.3% vs 76.5%) and overall survival (94.6% vs 90.3%) among locoregionally advanced NPC patients , as compared with chemoradiotherapy alone. Therefore, GP regimen has been established as the highest level of evidence-based induction chemotherapy in the 2020 National Comprehensive Cancer Network (NCCN) guidelines. Despite this intensified treatment approach, 20-30% of patients still have disease recurrences, highlighting the need for novel treatments in this population. Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. So we hypothesize that GP induction chemotherapy combined with toripalimab could further improve survival of patients with locoregionally advanced NPC. The goal of this randomized, double-blind, controlled phase III clinical trial is to evaluate the efficacy and safety of the GP induction chemotherapy combined with toripalimab or placebo , followed by concurrent chemoradiotherapy ± adjuvant metronomic capecitabine in patients with high-risk locoregionally advanced nasopharyngeal carcinoma.

Conditions

• Nasopharyngeal Carcinoma (NPC)

Interventions

Type	Name	Description
DRUG	TORIPALIMAB INJECTION (JS001 ) combine with GP chemotherapy	Drug: Toripalimab 240mg will be given every 3 weeks for 3 cycles, started on day 1 of induction chemotherapy. Other Names: JS001 PD-1 antibody Drug: Gemcitabine 1000mg/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation. Drug: Cisplatin Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 3 cycles during radiation Other Names: DDP Radiation: intensity-modulated radiotherapy Definitive intensity-modulated radiotherapy (IMRT) of 70 Gy will be given in 33 fractions. Other Names: IMRT
DRUG	GP plus placebo induction therapy	Drug: Placebo 240mg will be given every 3 weeks for 3 cycles, started on day 1 of induction chemotherapy. Drug: Gemcitabine 1000mg/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation. Drug: Cisplatin Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 3 cycles during radiation Other Names: DDP Radiation: intensity-modulated radiotherapy Definitive intensity-modulated radiotherapy (IMRT) of 70 Gy will be given in 33 fractions. Other Names: IMRT

Timeline

• Start date: 2025-02-17
• Primary completion: 2030-01-01
• Completion: 2032-01-01
• First posted: 2024-12-02
• Last updated: 2025-03-18

Locations

1 site across 1 country: China