NCT06455410

GP Plus Adebrelimab Versus GP Neoadjuvant Chemotherapy for Nasopharyngeal Carcinoma

GP Plus Adebrelimab Versus GP Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiotherapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 216 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to explore the efficacy and safety of neoadjuvant GP chemotherapy plus adebrelimab versus neoadjuvant GP chemotherapy in treating high-risk locoregionally advanced nasopharyngeal carcinoma patients.

Detailed description

Platinum-based neoadjuvant chemotherapy plus concurrent chemoradiotherapy (CCRT) 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. Three cycles of GP neoadjuvant chemotherapy resulted in 10% of complete response rate, and GP neoadjuvant 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 concurrent chemoradiotherapy alone. Therefore, GP has been established as the highest level of evidence-based neoadjuvant chemotherapy regimen in the 2020 National Comprehensive Cancer Network (NCCN) guidelines. Recently, immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) monoclonal antibody has shown promising efficacy in NPC patients. Clinical trials have shown objective response rates of 20.5%-34% in patients with recurrent or metastatic NPC patients receiving anti PD-1 monoclonal antibody immunotherapy including pembrolizumab, nivolumab, camrelizumab, and toripalimab. GP chemotherapy combined with anti PD-1 antibody were hence considered in treating locoregionally advanced NPC. Concurrent radiotherapy might cause T-cell dysfunction, and larger-volume elective nodal irradiation might hinder immunotherapy effects by directly depleting memory T cells. No survival benefit was observed when PD-1 blockade was added concurrently to the CCRT phase for treating head and neck cancers. On the contrary, several studies have demonstrated that administration of immunotherapy in the neoadjuvant setting modified the primary tumor into an antigen source for T-cell expansion and priming, thereby resulting in stronger effects than those of adjuvant therapy. Currently there were 3 trials exploring the addition of immunotherapy to chemoradiotherapy, the preliminary results of which were recently published. These trials had different trial designs, with two trials utilized anti PD-1 inhibitors in all treatment phases including neoadjuvant, concurrent and adjuvant phases, The third trial, which was conducted by our team, gave anti PD-1 inhibitor only in the neoadjuvant phase, and promising efficacy was observed in our study. Adebrelimab is a recombinant humanized IgG4 monoclonal antibody with specificity for PD-L1. In a phase III clinical trial of extensive stage small-cell lung cancer, the addition of adebrelimab significantly improved the median overall survival compared with the control group (15.3 vs. 12.8，HR 0.72, P=0.0017). So we hypothesize that GP neoadjuvant chemotherapy combined with adebrelimab could further improve the survival of patients with high-risk locoregionally advanced NPC (diagnosed with T4 or N2-3 disease). Therefore, we designed this phase II multi-center randomized controlled trial to evaluate whether GP neoadjuvant chemotherapy combined with adebrelimab plus cisplatin-based CCRT improve the complete response rate of high-risk locoregionally advanced NPC patients compared with GP neoadjuvant chemotherapy plus CCRT.

Conditions

• Nasopharyngeal Carcinoma

Interventions

Type	Name	Description
DRUG	GP	gemcitabine + cisplatin
DRUG	Adebrelimab	a PD-L1 inhibitor
DRUG	concurrent chemoradiotherapy (CCRT)	concurrent chemoradiotherapy (CCRT)

Timeline

• Start date: 2024-06-18
• Primary completion: 2026-06-18
• Completion: 2028-06-18
• First posted: 2024-06-12
• Last updated: 2024-06-25

Locations

12 sites across 1 country: China