Neoadjuvant Low-Dose Radiotherapy Plus Targeted-Immunotherapy vs Targeted-Immunotherapy Monotherapy in Resectable HNSCC: A Randomized Trial

Phase 2

Recruiting

• Conditions: Head and Neck Cancer
• Interventions: Drug: Tislelizumab; Drug: Afatinib; Radiation: Low dose radiotherapy

• Registration Number: NCT06804850
• Lead Sponsor: West China Hospital

Brief Summary

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

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 Timeline

• Study Start: 2025-01-20
• Study First Submitted: 2025-01-27
• Study First Submitted QC: 2025-01-27
• Study First Posted: 2025-02-03
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-16
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 98

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.

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

9. 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.

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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Cohort	Tislelizumab	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
Treatment Cohort	Afatinib	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
Treatment Cohort	Low dose radiotherapy	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
Control Cohort	Tislelizumab	1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42 2. Standard of care surgery
Control Cohort	Afatinib	1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42 2. Standard of care surgery

Primary Outcome Measures

Name	Time	Method
Major Pathologic Response	Intraoperative	Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells.

Secondary Outcome Measures

Name	Time	Method
Pathologic Complete Response	Intraoperative	Pathologic Complete Response (pCR) was defined as the absence of viable tumor cells.
Objective Response Rate	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
Disease-free Survival	1 year	Disease-free Survival (DFS) was defined as the time from the administration of the first dose to first disease progression or death.
Progression-Free Survival	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.
Overall Survival	1 year	Overall Survival (OS) was defined as the time from the start of treatment initiation to the patient's death from any cause.
Immune microenvironment	Intraoperative	The local microenvironment of tumor cells, including the changes of T lymphocytes, B lymphocytes and other cells.

Trial Locations

Locations (1)

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China