Neoadjuvant low-dose radiation plus afatinib and tislelizumab versus afatinib and tislelizumab alone for operable head and neck cancer

A Prospective Randomized Controlled Trial Comparing Low-Dose Radiotherapy Combined With Targeted Therapy and Immunotherapy Versus Targeted Therapy and Immunotherapy Alone as Neoadjuvant Therapy in Patients With Operable Head and Neck Squamous Cell Carcinoma.

We are testing whether adding low-dose radiotherapy before surgery to afatinib plus tislelizumab helps adults with resectable head and neck squamous cell carcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 98 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: West China Hospital (Academic / other)
• Drugs / interventions: immunotherapy, Tislelizumab, Afatinib, chemotherapy
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT07040956 on ClinicalTrials.gov

What this trial studies

This Phase 2 comparison gives some patients a short course of low-dose radiotherapy together with afatinib (an EGFR inhibitor) and tislelizumab (an anti–PD-1 antibody) before planned surgical resection, while others receive afatinib and tislelizumab alone. Eligible adults have pathologically confirmed, resectable head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma) and ECOG performance status 0–1. Key outcomes include radiographic and pathologic tumor response, rates of complete resection and organ preservation, and treatment safety. The approach aims to use low-dose radiotherapy to reprogram the tumor immune microenvironment and leverage high EGFR expression in HNSCC to improve neoadjuvant response.

Who should consider this trial

Good fit: Adults (≥18 years) with pathologically confirmed, newly diagnosed resectable head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma), ECOG 0–1, adequate organ function, and willing to undergo surgery are eligible.

Not a fit: Patients with distant metastases, unresectable tumors, poor performance status, significant organ dysfunction, or those unable/unwilling to have surgery are unlikely to benefit from this neoadjuvant regimen.

Why it matters

Potential benefit: If successful, this approach could increase tumor shrinkage before surgery, improve the chance of complete resection and organ preservation, and enhance anti-tumor immune effects.

How similar studies have performed: Early single-arm work combining low-dose radiotherapy with tislelizumab and afatinib has suggested safety and feasibility, and other studies show radiotherapy can synergize with PD‑1 blockade, but randomized neoadjuvant data remain limited.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years or above.
2. Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following condition:

   ①Were newly diagnosed and without distant metastasis; were deemed surgically resectable, evaluated by a head and neck surgeon;

   ②Were willing to undergo surgery;

   ③Eastern Cooperative Oncology Group (ECOG) performance status 0-1;

   ④Adequate 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.
3. 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 severe hypersensitivity reaction to drugs, or allergy to the study drug components.
4. Any of prior therapy with:

   ①anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； ②antitumor vaccine; ③any active vaccine against an infectious disease within 4 weeks before the first dose or planned during the study period; ④major surgery or serious trauma within 4 weeks before the first dose; ⑤toxicity 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.

Where this trial is running

Chengdu, Sichuan

• Department of Radiation Oncology — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Study coordinator: Xingchen Peng

Conditions Head and Neck Squamous Cell Carcinoma; Low-dose Radiotherapy; Immunotherapy; Targeted Therapy