Serplulimab Combined With Induction Chemotherapy and Radiotherapy in Nasopharyngeal Carcinoma

Официальное название

Induction Chemotherapy Combined With Serplulimab Induction/Maintenance Therapy and Omission of Concurrent Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma (UNION-NPC-001): A Multicenter, Open-Label, Randomized, Controlled, Phase III, Non-Inferiority Clinical Trial

Обзор

This phase III trial aims to evaluate the efficacy and safety of induction chemotherapy combined with serplulimab (induction/maintenance therapy) with omission of concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).

Подробное описание

This multicenter phase III trial enrolls high-risk locally advanced nasopharyngeal carcinoma patients (AJCC 9th edition, Stage T1-3N2 \[II\] or T1-4N3/T4N1-2 \[III\]) who achieves ≥50% tumor regression (RECIST v1.1) and undetectable plasma EBV DNA after three cycles of GP induction chemotherapy (gemcitabine + cisplatin) combined with serplulimab. Eligible patients will be randomized to either:

Experimental arm: Radiotherapy alone followed by serplulimab maintenance, or Control arm: Cisplatin-based concurrent chemoradiotherapy (CCRT) followed by serplulimab maintenance.

Primary study endpoint

* 3-year event-free survival (EFS)

* 5-year overall survival (OS)

* incidence of treatment-induced vomiting Secondary study endpoints * 3-year distant metastasis-free survival (DMFS)

* 3-year locoregional recurrence-free survival (LRFS)

* Quality of life (QoL) assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30 v3.0) and its head-and-neck cancer module (EORTC QLQ-H\&N35 v1.0), both validated Chinese versions.

* Incidence rate of investigator-reported adverse events (AEs) ⑤ Incidence rate of patient-reported AEs

Вмешательства

• Лучевая терапия Radiotherapy
  Following induction therapy, eligible patients will receive radiotherapy alone or concurrent chemoradiotherapy per protocol. Photon or proton radiotherapy techniques were permitted. Prescribed doses were: Primary tumor and metastatic lymph nodes: 70 Gy/33 fractions High-risk lymphatic drainage areas: 60 Gy/33 fractions Low-risk regions: 54 Gy/33 fractions PTV dose specifications: GTVnx: 70 Gy GTVnd: 66-70 Gy (reducible to 63 Gy for suspicious small nodes) CTV1: 60-62 Gy CTV2: 54-56 Gy All tre
• Препарат Serplulimab
  Serplulimab will be used in the induction phase for 3 cycles and the maintenance phase for 14 cycles.
• Препарат Cisplatin
  On days 64 and 85, patients will receive cisplatin chemotherapy at a dose of 100 mg/m² via intravenous infusion.

Первичные конечные точки

• Event-free survival (EFS) [Срок оценки: 3-year]
• Overall survival (OS) [Срок оценки: 5-year]
• Incidence rate of all-grade vomiting [Срок оценки: Through study completion, an average of 1 year]

Вторичные конечные точки (6)

• Distant metastasis-free survival (DMFS) [Срок оценки: 3-year]
• Locoregional recurrence-free survival (LRFS) [Срок оценки: 3-year]
• Health-Related Quality of Life assessed by EORTC QLQ-C30 [Срок оценки: From baseline (at informed consent) up to 60 months after radiotherapy completion.]
• Head and Neck Cancer-Specific Symptoms assessed by EORTC QLQ-H&N35 [Срок оценки: From baseline (informed consent) until 60 months after radiotherapy completion.]
• Incidence rate of investigator-reported adverse events (AEs) [Срок оценки: 3-year]
• Incidence rate of patient-reported adverse events (AEs) [Срок оценки: 3-year]

Критерии участия

Критерии включения

• Age at diagnosis: 18-65 years;
• Pathologically confirmed treatment-naïve nasopharyngeal carcinoma of "non-keratinizing type (WHO classification)";
• Locoregionally advanced nasopharyngeal carcinoma staged per the 9th edition of the American Joint Committee on Cancer (AJCC) staging system: Stage II (T1-3N2), Stage III(T1-4N3 or T4N1-2);
• ECOG performance status: 0-1;
• Post-induction therapy requirements:

Radiological assessment showing ≥50% tumor regression (RECIST 1.1) Undetectable plasma EBV DNA levels;

• Adequate bone marrow function:

White blood cell count >4×10⁹/L Hemoglobin >90 g/L Platelet count >100×10⁹/L;

• Normal hepatic/renal function:

Total bilirubin ≤1.5×upper limit of normal (ULN) AST/ALT ≤2.5×ULN Alkaline phosphatase ≤2.5×ULN Creatinine clearance ≥60 mL/min;

• Normal results for:

Thyroid function tests Amylase and lipase Pituitary function Inflammatory/infection markers Cardiac enzymes Electrocardiogram

Additional requirements:

Pulmonary function tests for smokers >50 years Cardiac ultrasound + myocardial function tests for patients with ECG abnormalities or cardiovascular history (unless meeting exclusion criterion (8));

• Signed informed consent with willingness/compliance to follow study schedules for treatment, follow-up, and laboratory tests;
• For women of childbearing potential: Agreement to use reliable contraception (e.g., condoms, prescribed oral contraceptives) from screening until 1 year post-treatment.

Критерии исключения

• Hepatitis B Virus (HBV) Infection:

HBsAg-positive with HBV DNA >1×10³ copies/mL (patients with controlled viremia \[<1×10³ copies/mL\] after antiviral therapy are eligible).

• Hepatitis C Virus (HCV) Infection: Anti-HCV antibody-positive.
• HIV/AIDS: Anti-HIV antibody-positive or diagnosed with acquired immunodeficiency syndrome (AIDS).
• Active Tuberculosis (TB): History of active TB within the past year (regardless of treatment status). Exception: Patients with adequately treated past TB (confirmed by standard anti-TB therapy) may be enrolled if >1 year since completion of treatment.
• Active Autoimmune Diseases:Known or suspected autoimmune disorders (e.g., uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, hypothyroidism, or asthma requiring bronchodilators).

Exceptions:

Type 1 diabetes mellitus Hypothyroidism managed with hormone replacement Skin conditions not requiring systemic therapy (e.g., vitiligo, psoriasis, alopecia).

• Interstitial Lung Disease (ILD):

History of ILD or pneumonitis requiring oral/IV steroids within the past year.

• Immunosuppressive Therapy:

Chronic systemic corticosteroids (≥10 mg prednisone equivalent/day) or other immunosuppressants within 4 weeks prior to enrollment. Inhaled/topical steroids are permitted.

• Uncontrolled Cardiac Disease: Heart failure (NYHA class ≥2), Unstable angina, Myocardial infarction within the past year, Clinically significant arrhythmias requiring treatment.
• Pregnancy/Lactation: Pregnant or breastfeeding women (urine/blood pregnancy test required for women of childbearing potential).
• Concurrent Malignancies:

History of other malignancies except:

Adequately treated non-melanoma skin cancer, Carcinoma in situ of the cervix, Papillary thyroid carcinoma.

• Hypersensitivity: Known allergy to any component of the study drugs or excipients.
• Active Infections:

Systemic infections requiring treatment within 1 week prior to enrollment.

Live Vaccines:

• Administration of live vaccines within 30 days before the first immunotherapy dose.
• Organ Transplantation: History of allogeneic organ transplantation.
• Other High-Risk Conditions:

Any condition that may compromise patient safety or compliance per investigator assessment (e.g., severe psychiatric disorders, life-threatening comorbidities, or social/familial risk factors).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Wuhan Union Hospital — Ухань

Идентификаторы

NCT: NCT07177443 · UNION-NPC-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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