Neoadjuvant Radio-immunotherapy Versus Immunotherapy Alone for Locally Advanced HNSCC

Официальное название

A Randomized, Controlled, Phase II Clinical Study of Neoadjuvant Radio-immunotherapy Versus Immunotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Обзор

The purpose of this randomized Phase II study is to evaluate and compare the efficacy and safety of neoadjuvant radio-immunotherapy versus immunotherapy alone for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Participants will be randomly assigned to one of two groups. The experimental group will receive a combination of radiotherapy and Adebrelimab as neoadjuvant treatment, while the control group will receive Adebrelimab monotherapy. Following the neoadjuvant phase, all eligible patients will undergo surgical resection. The primary objective is to determine if the addition of radiotherapy improves the major pathological response (MPR) rate. Secondary objectives include pathological complete response (pCR) rate, objective response rate (ORR), and event-free survival (EFS).

Подробное описание

This is a randomized, controlled, open-label, Phase II clinical trial designed to compare the efficacy and safety of neoadjuvant radiotherapy combined with Adebrelimab versus Adebrelimab monotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Experimental Arm (Radio-immunotherapy): Patients will receive neoadjuvant radiotherapy (SBRT 24 Gy in 3 fractions) followed by or concurrent with 2 cycles of Adebrelimab (1200mg, Q3W).

Control Arm (Immunotherapy alone): Patients will receive 2 cycles of Adebrelimab (1200mg, Q3W) as monotherapy.

Following the completion of neoadjuvant therapy, a multidisciplinary team (MDT) will evaluate the patients' response. Eligible patients will then undergo standard surgical resection of the primary tumor and neck dissection within 3 to 4 weeks after the last dose of immunotherapy.

The primary endpoint is the Major Pathological Response (MPR) rate, defined as less than or equal to 10% residual viable tumor in the resected specimen. Secondary endpoints include Pathological Complete Response (pCR) rate, Objective Response Rate (ORR) according to RECIST 1.1, Event-Free Survival (EFS), and the incidence of treatment-emergent adverse events (TEAEs) graded by CTCAE 5.0.

Вмешательства

• Препарат Adebrelimab
  A humanized IgG4 monoclonal antibody against programmed cell death-ligand 1 (PD-L1). Dosage: 1200 mg administered via intravenous (IV) infusion on Day 1 of each 21-day cycle, for a total of 2 cycles in the neoadjuvant setting.
• Лучевая терапия radiotherapy
  Neoadjuvant radiotherapy targeting the primary tumor and involved cervical lymph nodes. (SBRT with a total dose of \[24\] Gy in \[3\] fractions).

Первичные конечные точки

• Major Pathological Response (MPR) Rate [Срок оценки: At the time of surgery (approximately 6-8 weeks after the first dose of neoadjuvant therapy).]

Вторичные конечные точки (3)

• Pathological Complete Response (pCR) Rate [Срок оценки: At the time of surgery.]
• Objective Response Rate (ORR) [Срок оценки: From the first dose of neoadjuvant therapy until pre-operative clinical evaluation (approximately 6 weeks).]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: From the start of treatment up to 30 days after surgery.]

Критерии участия

Критерии включения

• Histologically confirmed, treatment-naive, resectable head and neck squamous cell carcinoma (HNSCC).
• Clinical stage III to IVB (according to AJCC 8th edition), excluding HPV-positive oropharyngeal cancer.
• PD-L1 expression with a Combined Positive Score (CPS) ≥ 1.
• Karnofsky Performance Status (KPS) score ≥ 70.
• Age between 18 and 70 years (inclusive).
• Evaluated by a multidisciplinary team (MDT) as resectable or borderline resectable, and suitable for preoperative Stereotactic Body Radiotherapy (SBRT).
• Adequate organ function within 7 days prior to enrollment, meeting laboratory criteria for hematology, liver, and renal function.
• Anatomical requirements for SBRT: Lesions must be localized with adequate anatomical space for high-precision radiotherapy without exceeding safety limits for Organs at Risk (OARs).
• Voluntary participation with a signed Informed Consent Form (ICF).

Критерии исключения

• Prior radical surgery, radiotherapy, or immunotherapy for head and neck malignancies.
• Severe comorbidities that may interfere with study participation, such as uncontrolled cardiovascular disease or active infections.
• Active Hepatitis B virus (HBV) infection (HBsAg positive and HBV DNA ≥ 500 IU/mL).
• Pregnant or breastfeeding women.
• Any other condition that, in the opinion of the investigator, makes the patient unsuitable for enrollment.

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

• Sun Yat-sen University Cancer Center — Гуанчжоу

Идентификаторы

NCT: NCT07554768 · B2026-158-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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