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

NCT06804850 | Withdrawn Phase 2

• 1 other identifier: 2025-196
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response

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

  Intraoperative

Secondary Outcomes (6)

• Pathologic Complete Response

  Intraoperative

• Objective Response Rate

  Up to 8 weeks

• Disease-free Survival

  1 year

• Progression-Free Survival

  1 year

• Overall Survival

  1 year

Study Arms (2)

Treatment Cohort

EXPERIMENTAL

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; Drug: Afatinib; Radiation: Low dose radiotherapy

Control Cohort

ACTIVE COMPARATOR

1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42 2. Standard of care surgery

Drug: Tislelizumab; Drug: Afatinib

Interventions

Tislelizumab DRUG

200mg IV Q3W

Also known as: Immunotherapy

Control Cohort; Treatment Cohort

Afatinib DRUG

30mg PO QD

Also known as: Targeted therapy

Control Cohort; Treatment Cohort

Low dose radiotherapy RADIATION

4Gy / 2f. Intensity-modulated radiotherapy was used for radiotherapy.

Also known as: Radiotherapy

Treatment Cohort

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:
• ◦ were newly diagnosed and without distant metastasis; were deemed surgically
• resectable evaluated by a head and neck surgeon;
• were willing to undergo surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• 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.
• 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 sever 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. 8. 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. 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.
• \. 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

Related Publications (9)

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• Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010;15(9):994-1001. doi: 10.1634/theoncologist.2009-0289. Epub 2010 Aug 26.

  PMID: 20798198 BACKGROUND

• Denaro N, Merlano MC, Russi EG. Follow-up in Head and Neck Cancer: Do More Does It Mean Do Better? A Systematic Review and Our Proposal Based on Our Experience. Clin Exp Otorhinolaryngol. 2016 Dec;9(4):287-297. doi: 10.21053/ceo.2015.00976. Epub 2016 Jun 25.

  PMID: 27337948 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

Head and Neck Neoplasms

Interventions

tislelizumab; Immunotherapy; Afatinib; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

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

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: January 27, 2025
• First Posted: February 3, 2025
• Study Start: January 20, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share