Head and Neck Squamous Cell Carcinoma, Locally Advanced Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Neoadjuvant Therapy, Radio-immunotherapy, Adebrelimab, PD-L1 Inhibitor, SBRT
Brief summary
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).
Detailed description
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.
Interventions
DRUGAdebrelimab
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.
RADIATIONradiotherapy
Neoadjuvant radiotherapy targeting the primary tumor and involved cervical lymph nodes. (SBRT with a total dose of \[24\] Gy in \[3\] fractions).
Sponsors
Chen Chunyan
Shanghai Shengdi Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Although the study is open-label due to the nature of radiotherapy intervention, the pathological assessment of the primary endpoint (Major Pathological Response, MPR) will be performed by independent pathologists who are masked to the treatment assignment to minimize bias.
Intervention model description
This is a randomized, open-label, two-arm, parallel-assignment Phase II study. Eligible patients with locally advanced HNSCC will be randomized at a 1:1 ratio to receive either neoadjuvant Adebrelimab in combination with radiotherapy (Experimental Arm) or Adebrelimab monotherapy (Control Arm). Randomization will be stratified by \[stratification factors, e.g., clinical stage (III vs. IV) or primary tumor site\]. Both groups will undergo surgical resection following the completion of neoadjuvant therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed, treatment-naive, resectable head and neck squamous cell carcinoma (HNSCC). 2. Clinical stage III to IVB (according to AJCC 8th edition), excluding HPV-positive oropharyngeal cancer. 3. PD-L1 expression with a Combined Positive Score (CPS) ≥ 1. 4. Karnofsky Performance Status (KPS) score ≥ 70. 5. Age between 18 and 70 years (inclusive). 6. Evaluated by a multidisciplinary team (MDT) as resectable or borderline resectable, and suitable for preoperative Stereotactic Body Radiotherapy (SBRT). 7. Adequate organ function within 7 days prior to enrollment, meeting laboratory criteria for hematology, liver, and renal function. 8. 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). 9. Voluntary participation with a signed Informed Consent Form (ICF).
Exclusion criteria
1. Prior radical surgery, radiotherapy, or immunotherapy for head and neck malignancies. 2. Severe comorbidities that may interfere with study participation, such as uncontrolled cardiovascular disease or active infections. 3. Active Hepatitis B virus (HBV) infection (HBsAg positive and HBV DNA ≥ 500 IU/mL). 4. Pregnant or breastfeeding women. 5. Any other condition that, in the opinion of the investigator, makes the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response (MPR) Rate | At the time of surgery (approximately 6-8 weeks after the first dose of neoadjuvant therapy). | The percentage of participants with 10% or less residual viable tumor cells in the resected primary tumor and lymph nodes following neoadjuvant therapy. Assessment will be performed by independent pathologists. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | At the time of surgery. | The percentage of participants with no residual viable tumor cells (0%) in the resected primary tumor and lymph nodes. |
| Objective Response Rate (ORR) | From the first dose of neoadjuvant therapy until pre-operative clinical evaluation (approximately 6 weeks). | The percentage of participants with a complete response (CR) or partial response (PR) based on RECIST v1.1 criteria as assessed by imaging (CT or MRI) prior to surgery. |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | From the start of treatment up to 30 days after surgery. | Percentage of participants with treatment-emergent adverse events (TEAEs) as defined by CTCAE v5.0. Adverse events include immune-related adverse events (irAEs) and radiation-related toxicities. Severity will be graded for each event according to CTCAE v5.0 criteria. |
Countries
China
Contacts
CONTACTAnqi He, MB
CONTACTChunyan Chen, MD
PRINCIPAL_INVESTIGATORChunyan Chen
Sun Yat-Sen University Cancer Center
Outcome results
None listed