This study is a multicenter, randomized, controlled phase III clinical trial aiming to investigate the efficacy and safety of Becotatug Vedotin induction therapy followed by concurrent chemoradiotherapy (CCRT) combined with neoadjuvant and adjuvant sintilimab, versus gemcitabine plus cisplatin (GP) induction chemotherapy followed by CCRT, in the treatment of high-risk locally advanced nasopharyngeal carcinoma (LANPC). The study plans to enroll 266 patients with high-risk NPC (AJCC 9th edition, anyT N2-3M0 or T4N1M0), who will be randomly assigned to the experimental group or the control group at a 1:1 ratio.The primary endpoint is 3-year event-free survival (EFS), and the secondary endpoints include overall survival (OS), local-regional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), objective response rate (ORR), adverse events, and quality of life.
Voluntarily participate in the study and sign the informed consent form in writing.
Aged 18-70 years, male or non-pregnant female.
Pathologically confirmed as nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated type, i.e., WHO type II or III).
Staged as anyT N2-3 or T4N1 (9th AJCC/UICC staging) without distant metastasis.
Aged > 70 years or < 18 years.
Patients with recurrent or distant metastatic nasopharyngeal carcinoma.
Pathologically confirmed as keratinizing squamous cell carcinoma (WHO type I).
Patients who have previously received radiotherapy or systemic chemotherapy.
Parallel
Becotatug Vedotin
DrugBecotatug vedotin 2.3 mg/kg will be given on Day 1 of induction therapy, once every 3 weeks for a total of 3 cycles.
Sintilimab
DrugIn the induction treatment phase, sintilimab 200 mg will be administered on Day 1 of each induction cycle, once every 3 weeks, for a total of 3 cycles. In the adjuvant treatment phase, sintilimab 200 mg will be given on Day 1, initiated 3 weeks after the completion of radiotherapy, once every 3 weeks, for a total of 9 cycles.
Cisplatin
DrugConcurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
intensity-modulated radiotherapy
RadiationDefinitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions
Gemcitabine (GEM)
DrugGemcitabine 1g/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation.
Cisplatin
DrugInduction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation
Event-free survival (EFS)
The time interval from randomization to the first treatment failure or the last follow-up if there is no treatment failure. Treatment failure is defined as local/cervical residual disease 16 weeks after radiotherapy, local/cervical recurrence, distant metastasis, or death due to any cause,whichever occurred first.
Overall survival (OS)
The time interval from randomization to the date of death from any cause.
Distant metastasis-free survival (DMFS)
The time interval from randomization to the date of first distant metastasis, or death from any cause, whichever occurred first.
Locoregional recurrence-free survival (LRFS)
The time interval randomization to the date of locoregional persistence, 1st locoregional recurrence, or death from any cause, whichever occurred first.
Adverse events (AEs) and serious adverse events (SAEs)
Graded according to CTCAE V5.0.
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First Affiliated Hospital of Guangxi Medical University
Lead sponsor
Xiangya Hospital of Central South University
Collaborator
First Affiliated Hospital of Fujian Medical University
Collaborator
Nanfang Hospital, Southern Medical University
Collaborator
Hunan Provincial Cancer Hospital
Collaborator
Affiliated Hospital of North Sichuan Medical College
Collaborator
First Hospital of China Medical University
Collaborator
Guangdong Provincial People's Hospital
Collaborator
First People's Hospital of Yulin
Collaborator
Wuzhou Red Cross Hospital
Collaborator
LiuZhou People's Hospital
Collaborator
