Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

All Conditions

Rare Diseases

Nasopharyngeal Carcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Tislelizumab

Cisplatin

Immunomodulating Agents

Antineoplastic Agents, Immunological

Patients receive neoadjuvant therapy with gemcitabine(1000mg per square meter on day 1,8) , cisplatin (80mg per square meter on day 1) and tislelizumab(200mg) every three weeks for three cycles before radiotherapy, then followed by concurrent IMRT and cisplatin (100mg per square meter) concurrent every three weeks during radiotherapy (D1,D22,D43 of RT) .

chemotherapy combine with anti-PD-1 targeted immunotherapy+concurrent chemotherapy

GP combine with Tislelizumab neoadjuvant therapy+CCRT

Hai qiang Mai

Lin quan Tang

Hai-Qiang Mai, MD

Su LI, MD

The purpose of this study is to explore the efficacy and safety of a combination of GP chemotherapy and tislelizumab in neoadjuvant therapy of locoregionally advanced nasopharyngeal carcinoma patients.

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 neoadjuvant chemotherapy, 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 chemoradiotherapy alone. Therefore, GP regimen has been established as the highest level of evidence-based neoadjuvant chemotherapy 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 the treatment of tumor 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. The current NCCN guidelines recommend anti PD-1 monoclonal antibody as a second-line treatment for recurrent or metastatic NPC. More and more evidence show that immunotherapy combined with chemotherapy has a synergistic effect in treating tumors. GP chemotherapy combined with anti PD-1 antibody has achieved the initial effect in NPC. Phase 1 trials have shown the combination of camrelizumab plus GP chemotherapy in recurrent or metastatic NPC led to a proportion of 91% patients achieving an objective response. Tislelizumab, approved by the National Medical Products Administration in China, is an anti-PD-1 monoclonal IgG4 antibody with higher affinity to PD-1 than pembrolizumab and nivolumab and was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Multiple clinical trials have shown strong anti-neoplastic activity of tislelizumab in various tumors including NPC. Clinical trial has shown an objective response rates of 43% in patients with recurrent metastatic nasopharyngeal carcinoma treated with tirelizumab, which is superior to other anti PD-1 monoclonal antibodys. So we hypothesize that GP neoadjuvant chemotherapy combined with tislelizumab could further improve survival of patients with locaregionally advanced NPC. Based on this, this study aims to evaluate the efficacy and safety of gemcitabine plus cisplatin chemotherapy combined with tislelizumab neoadjuvant therapy, followed by cisplatin based concurrent chemoradiotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma, to provide new evidence for individualized comprehensive treatment in NPC.

Neoadjuvant Therapy of GP Chemotherapy Combined With Tislelizumab in Locoregionally Advanced NPC

Efficacy and Safety of of GP Chemotherapy Combined With Tislelizumab Neoadjuvant Therapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: a Single-arm, Phase 2 Trial

CR assessed by independent reviewers, according to the Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the neoadjuvant therapy. Complete response defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) .

Pathological complete response defined as the complete disappearance of the tumor cells in biopsy tissue of nasopharynx after neoadjuvant therapy .

The OS was defined as the duration from the date of registration to the date of death from any cause or censored at the date of the last follow-up.

Progress-free survival is calculated from the date of registration to the date of the first progress at any site or death from any cause or censored at the date of the last follow-up

The LRRFS is evaluated and calculated from the date of registration until the day of first locoregional relapse or until the date of the last follow-up visit.

The DMFS is evaluated and calculated from the date of registration until the day of first distant metastases or until the date of the last follow-up visit.

Analysis of treatment-related AEs (trAEs) and immune-related AEs (irAEs) are evaluated on basis of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Therapy of GP Chemotherapy Combined With Tislelizumab in Locoregionally Advanced NPC	NCT04833257	Nasopharyngeal ...	GP combine with...	18 Years - 70 Years	Sun Yat-sen University
Neoadjuvant Therapy of GP Chemotherapy Combined With Tislelizumab in Locoregionally Advanced NPC	NCT04833257	Nasopharyngeal ...	GP combine with...	18 Years - 70 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for gp combine with tislelizumab neoadjuvant therapy+ccrt