NCT07371234

Low-Dose Radiotherapy and Anti-PD-1 Immunotherapy as Neoadjuvant Treatment for Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

A Single Arm, Phase II Clinical Study of Low-Dose Radiotherapy Combined With Anti-PD-1 Monoclonal Antibody Immunotherapy as Neoadjuvant Treatment for Surgically Resectable, Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Sponsor: Xiwei XU · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Over 60% of head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at a locally advanced stage. While standard treatments involve surgery and chemoradiotherapy, prognosis remains poor, with 50-60% experiencing local recurrence within two years. Neoadjuvant therapy can potentially reduce tumor burden, preserve organs, and lower distant metastasis risk. Despite the KEYNOTE-689 trial showing that adjuvant two-cycle pembrolizumab increased major pathological response to 9.8% in stage III-IVB HNSCC, this result remains insufficient. More effective immunotherapy-based combinations are urgently needed to improve long-term survival after neoadjuvant treatment. Preclinical and clinical evidence indicates that low-dose radiotherapy can activate the tumor immune microenvironment and synergize with immunotherapy. Based on this rationale, the present clinical trial will evaluate a neoadjuvant regimen combining LDRT with two cycles of an anti-PD-1 inhibitor in patients with surgically resectable, locally advanced HNSCC.

Conditions

• Locally Advanced Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Neoadjuvant and Adjuvant Immunotherapy	Neoadjuvant therapy with Toripalimab (240mg, Day 1, Q3W, 2 cycles);Adjuvant immunotherapy with Toripalimab (240mg, Day 1, Q3W, for a total of 15 cycles).
RADIATION	Low-dose radiotherapy	Low-dose radiotherapy (1 Gy/fraction, on Days 1, 8, and 15 of each cycle, Q3W, for 2 cycles; total dose: 6 Gy in 6 fractions).
PROCEDURE	Surgery	Radical surgery performed 3-4 weeks after neoadjuvant therapy, following a re-evaluation of surgical indications by the surgeon.
RADIATION	Adjuvant Radiotherapy	Low-risk group: 60 Gy in 30 fractions, using intensity-modulated radiation therapy (IMRT); High-risk group: 66 Gy in 33 fractions, or 70 Gy in 35 fractions for residual lesions, using intensity-modulated radiation therapy (IMRT).
DRUG	Adjuvant Cisplatin	High-risk group：Cisplatin 100 mg/m² is administered via intravenous infusion on Day 1 of every 21-day cycle during radiotherapy, for a total of 3 cycles.

Timeline

• Start date: 2025-12-15
• Primary completion: 2027-01-15
• Completion: 2028-12-30
• First posted: 2026-01-27
• Last updated: 2026-02-03

Locations

1 site across 1 country: China