Neoadjuvant Radio-immunotherapy Versus Immunotherapy Alone for Locally Advanced HNSCC

NCT07554768 | Not Yet Recruiting Phase 2

• 1 other identifier: B2026-158-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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).

Conditions

Head and Neck Squamous Cell Carcinoma; Locally Advanced Head and Neck Squamous Cell Carcinoma

Keywords

Neoadjuvant Therapy; Radio-immunotherapy; Adebrelimab; PD-L1 Inhibitor; SBRT

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR) Rate

  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.

  At the time of surgery (approximately 6-8 weeks after the first dose of neoadjuvant therapy).

Secondary Outcomes (3)

• Pathological Complete Response (pCR) Rate

  At the time of surgery.

• Objective Response Rate (ORR)

  From the first dose of neoadjuvant therapy until pre-operative clinical evaluation (approximately 6 weeks).

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  From the start of treatment up to 30 days after surgery.

Other Outcomes (1)

• Changes in Tumor Microenvironment (TME) Immune Cell Populations

  Baseline (biopsy) and at the time of surgery (approximately 6 weeks).

Study Arms (2)

Neoadjuvant Radio-immunotherapy (Adebrelimab + RT)

EXPERIMENTAL

Patients will receive 2 cycles of neoadjuvant Adebrelimab (1200 mg, IV, Q3W) combined with radiotherapy (SBRT), followed by surgical resection.

Drug: Adebrelimab; Radiation: radiotherapy

Neoadjuvant Immunotherapy Monotherapy (Adebrelimab)

ACTIVE COMPARATOR

Patients will receive 2 cycles of neoadjuvant Adebrelimab (1200 mg, IV, Q3W) monotherapy, followed by surgical resection.

Drug: Adebrelimab

Interventions

Adebrelimab DRUG

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.

Neoadjuvant Immunotherapy Monotherapy (Adebrelimab); Neoadjuvant Radio-immunotherapy (Adebrelimab + RT)

radiotherapy RADIATION

Neoadjuvant radiotherapy targeting the primary tumor and involved cervical lymph nodes. (SBRT with a total dose of \[24\] Gy in \[3\] fractions).

Neoadjuvant Radio-immunotherapy (Adebrelimab + RT)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chen Chunyan: lead
• Shanghai Shengdi Pharmaceutical Co., Ltd: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Chunyan Chen

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anqi He, MB

CONTACT

+86-18025464619; heaq@sysucc.org.cn

Chunyan Chen, MD

CONTACT

+86-13826423812; chenchuny@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: April 28, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)