Neoadjuvant Radiotherapy Plus Targeted Therapy and Immunotherapy vs. Targeted Therapy Plus Immunotherapy in Resectable HNSCC

November 15, 2025 updated by: Xingchen Peng, West China Hospital

Neoadjuvant Low-Dose Radiotherapy Plus Targeted Therapy and Immunotherapy vs. Targeted Therapy Plus Immunotherapy in Resectable Head and Neck Squamous Cell Carcinoma: A Prospective Randomized Controlled Trial

This study compares the efficacy of neoadjuvant low-dose radiotherapy plus targeted-immunotherapy versus targeted-immunotherapy alone in resectable HNSCC patients.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor in the head and neck region. It has a high global incidence. Due to its special anatomical location, HNSCC affects patients' appearance and physiological functions. Comprehensive treatments such as surgery, radiotherapy, and chemotherapy are often adopted. More than 60% of patients are diagnosed with locally advanced or metastatic diseases, resulting in a low 5-year survival rate. Locally advanced patients have high recurrence and metastasis rates, and a poor prognosis. Neoadjuvant therapy before surgery theoretically can improve the possibility of radical surgery and the organ preservation rate. However, except for nasopharyngeal carcinoma, induction chemotherapy has not brought significant survival benefits to HNSCC patients, and new treatment regimens are urgently needed.

EGFR is overexpressed in 90% of HNSCC patients. The PD-1/PD-L1 signaling pathway is an important mechanism of tumor escape. Anti-PD-1/PD-L1 monoclonal antibodies have shown good efficacy and high safety in the treatment of malignant tumors. The combination of radiotherapy and immunotherapy can induce an anti-tumor immune response. Low-dose radiotherapy (LDRT) has low toxicity and can reprogram the tumor immune microenvironment. Multiple studies have confirmed the safety and feasibility of its combination with immunotherapy.

The previously conducted "Prospective, Single-arm Clinical Study of Low-dose Radiotherapy Plus Tislelizumab Combined with Afatinib for Neoadjuvant Therapy of Resectable Head and Neck Squamous Cell Carcinoma" has demonstrated good safety. Based on this, a head-to-head clinical study is planned to compare the efficacy of low-dose radiotherapy combined with targeted immunotherapy and pure targeted immunotherapy in patients with resectable head and neck squamous cell carcinoma, explore the clinical benefits of this new treatment measure, and provide new treatment options for HNSCC patients.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • Recruiting
        • West China Hospital, Sichuan University
        • Contact:
          • Xingchen Peng, PhD
          • Phone Number: 18980606753

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18 years or above.

  2. Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following condition:

    ◦ were newly diagnosed and without distant metastasis; were deemed surgically

    • resectable evaluated by a head and neck surgeon;
    • were willing to undergo surgery.
  3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

  4. Adequate organ and bone marrow function:

    • absolute neutrophil count ≥ 1.5 × 10^9/L, hemoglobin ≥ 80 g/L, platelets ≥ 80 × 10^9/L;
    • ALT, AST and ALP < 2.5× upper limit of normal (ULN), total bilirubin ≤ 2×ULN; albumin≥ 2.8 g/dL；
    • creatinine clearance ≥ 60 ml/min；
    • INR≤ 1.5, APTT≤ 1.5×ULN.
  5. Written informed consent.

Exclusion Criteria:

  1. History of other malignancies (except for the history of malignant tumors that have been cured and have not recurred within 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, in situ cervical cancer, and gastrointestinal mucosal cancer, etc.）
  2. Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.
  3. Any history of allergic disease, or a sever hypersensitivity reaction to drugs, or allergy to the study drug components.
  4. Any of prior therapy with:

（1）anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； （2）antitumor vaccine; （3）any active vaccine against an infectious disease within 4 weeks prior to the first dose or planned during the study period; （4）major surgery or serious trauma within 4 weeks before the first dose; toxicity from prior antitumor therapy has not recovered to ≤ CTCAE Version 5.0 Grade 1 or the level specified by the inclusion/exclusion criteria.

5. With serious medical diseases, such as grade II and above cardiac dysfunction (NYHA criteria), ischemic heart disease, supraventricular or ventricular arrhythmia, poorly controlled diabetes mellitus, poorly controlled hypertension, echocardiographic ejection fraction < 50%, etc.

6. With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or history of pulmonary tuberculosis infection that were not controlled by treatment.

7. With hyperthyroidism, or organic thyroid disease. 8. With active infection, or unexplained fever during the screening period or 48 hours before the first dose.

9. With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.

10. History of a clear neurological or psychiatric disorder. 11. History of drug abuse or alcohol abuse. 12. Women who are pregnant or breastfeeding, or have a reproductive plan from the screening period to 3 months after the end of the study, or have sex without contraceptive measures, or are unwilling to take appropriate contraceptive measures.

13. Received any investigational drug within 4 weeks prior to the first dose, or concurrently enrolled in another clinical trial.

14. Any other factors that are not suitable for inclusion in this study judged by investigators.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Cohort
  1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42
  2. Low-dose radiotherapy, 4Gy/2f,radiotherapy using intensity-modulated radiotherapy technology.
  3. Standard of care surgery
Drug: Tislelizumab
200mg IV Q3W
Other Names:
  • Immunotherapy
Drug: Afatinib
30mg PO QD
Other Names:
  • Targeted therapy
Radiation: Low dose radiotherapy
4Gy / 2f. Intensity-modulated radiotherapy was used for radiotherapy.
Other Names:
  • Radiotherapy
Active Comparator: Control Cohort
  1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42
  2. Standard of care surgery
Drug: Tislelizumab
200mg IV Q3W
Other Names:
  • Immunotherapy
Drug: Afatinib
30mg PO QD
Other Names:
  • Targeted therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathologic Response
Time Frame: Intraoperative
Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells.
Intraoperative

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free Survival
Time Frame: 1 year
Disease-free Survival (DFS) was defined as the time from the administration of the first dose to first disease progression or death.
1 year
Pathologic Complete Response
Time Frame: Intraoperative
Pathologic Complete Response (pCR) was defined as the absence of viable tumor cells.
Intraoperative
Objective Response Rate
Time Frame: Up to 8 weeks
Objective Response Rate (ORR) was defined as the percentage of participants with a best overall response of CR or PR using RECIST Criteria
Up to 8 weeks
Progression-Free Survival
Time Frame: 1 year
Progression-Free Survival (PFS) was defined as the time from the commencement of therapy to the first evidence of disease progression or death.
1 year
Overall Survival
Time Frame: 1 year
Overall Survival (OS) was defined as the time from the start of treatment initiation to the patient's death from any cause.
1 year
Immune microenvironment
Time Frame: Intraoperative
The local microenvironment of tumor cells, including the changes of T lymphocytes, B lymphocytes and other cells.
Intraoperative

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 20, 2025

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

January 27, 2025

First Submitted That Met QC Criteria

January 27, 2025

First Posted (Actual)

February 3, 2025

Study Record Updates

Last Update Posted (Actual)

November 19, 2025

Last Update Submitted That Met QC Criteria

November 15, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-196

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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