A Clinical Trial Comparing Low-Dose RT + Targeted Therapy+ Immunotherapy vs Targeted Therapy+ Immunotherapy Alone as Neoadjuvant Therapy in Operable HNSCC Patients.

NCT07040956 | Recruiting Phase 2

• 1 other identifier: 2025 (196)
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to compare the efficacy of neoadjuvant low-dose radiotherapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone in patients with resectable head and neck squamous cell carcinoma.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response

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

  Intraoperative

Secondary Outcomes (2)

• Pathologic Complete Response

  Intraoperative

• Objective Response Rate

  From the start of neoadjuvant therapy to the end of neoadjuvant therapy, the duration is approximately 2 months.

Other Outcomes (2)

• To explore the dynamic changes in intratumoral biomarkers to evaluate the biological activity in patients receiving low-dose radiotherapy combined with targeted and immunotherapy compared with targeted and immunotherapy alone.

  Baseline through post-surgical pathological specimen acquisition (approximately to 12 weeks).

• To assess blood-based biomarkers in patients receiving low-dose radiotherapy combined with targeted and immunotherapy compared with targeted and immunotherapy alone.

  Baseline through post-surgical pathological specimen acquisition (approximately to 12 weeks).

Study Arms (2)

Low-dose radiotherapy + Immunotherapy + Targeted therapy

EXPERIMENTAL

1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42. 2. Low-dose radiotherapy, 4Gy/2f. 3. Surgery.

Drug: Tislelizumab; Drug: Afatinib; Radiation: Low dose radiotherapy

Immunotherapy + Targeted therapy

ACTIVE COMPARATOR

1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42 2. Surgery.

Drug: Tislelizumab; Drug: Afatinib

Interventions

Tislelizumab DRUG

200mg ivgtt q3w

Also known as: Immunotherapy

Immunotherapy + Targeted therapy; Low-dose radiotherapy + Immunotherapy + Targeted therapy

Afatinib DRUG

Targeted therapy

Also known as: 30mg po qd

Immunotherapy + Targeted therapy; Low-dose radiotherapy + Immunotherapy + Targeted therapy

Low dose radiotherapy RADIATION

Radiotherapy

Also known as: 4Gy / 2f

Low-dose radiotherapy + Immunotherapy + Targeted therapy

Eligibility Criteria

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

You may qualify if:

• Age 18 years or above.
• 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.
• Written informed consent.

You may not qualify if:

• 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.）
• Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.
• Any history of allergic disease, or a severe hypersensitivity reaction to drugs, or allergy to the study drug components.
• Any of prior therapy with:
• 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.
• With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or history of pulmonary tuberculosis infection that were not controlled by treatment.
• With hyperthyroidism, or organic thyroid disease.
• With active infection, or unexplained fever during the screening period or 48 hours before the first dose.
• With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.
• History of a clear neurological or psychiatric disorder.
• History of drug abuse or alcohol abuse.
• 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.
• Received any investigational drug within 4 weeks prior to the first dose, or concurrently enrolled in another clinical trial.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

Department of Radiation Oncology

Chengdu, Sichuan, 610000, China

RECRUITING

Related Publications (6)

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Harari PM. Promising new advances in head and neck radiotherapy. Ann Oncol. 2005;16 Suppl 6:vi13-vi19. doi: 10.1093/annonc/mdi453.

  PMID: 15987991 BACKGROUND

• Haddad R, O'Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, Clark J, Sarlis N, Lorch J, Beitler JJ, Limaye S, Riley S, Posner M. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013 Mar;14(3):257-64. doi: 10.1016/S1470-2045(13)70011-1. Epub 2013 Feb 13.

  PMID: 23414589 BACKGROUND

• Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, Brockstein BE, Agulnik MB, Mittal BB, Yunus F, Samant S, Raez LE, Mehra R, Kumar P, Ondrey F, Marchand P, Braegas B, Seiwert TY, Villaflor VM, Haraf DJ, Vokes EE. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol. 2014 Sep 1;32(25):2735-43. doi: 10.1200/JCO.2013.54.6309. Epub 2014 Jul 21.

  PMID: 25049329 BACKGROUND

• Geoffrois L, Martin L, De Raucourt D, Sun XS, Tao Y, Maingon P, Buffet J, Pointreau Y, Sire C, Tuchais C, Babin E, Coutte A, Rolland F, Kaminsky MC, Alfonsi M, Lapeyre M, Saliou M, Lafond C, Jadaud E, Gery B, Zawadi A, Tourani JM, Khoury C, Henry AR, Hasbini A, Guichard F, Borel C, Meert N, Guillet P, Calais MH, Garaud P, Bourhis J. Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial. J Clin Oncol. 2018 Nov 1;36(31):3077-3083. doi: 10.1200/JCO.2017.76.2591. Epub 2018 Jul 17.

  PMID: 30016178 BACKGROUND

• Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015 May;16(5):583-94. doi: 10.1016/S1470-2045(15)70124-5. Epub 2015 Apr 16.

  PMID: 25892145 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

tislelizumab; Immunotherapy; Afatinib; 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)

Immunomodulation; Biological Therapy; Therapeutics; Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Xingchen Peng

CONTACT

18980606753; pxx2014@163.com

Study Design

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

Study Record Dates

• First Submitted: June 19, 2025
• First Posted: June 27, 2025
• Study Start: June 28, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)