Locally Advanced Head and Neck Squamous Cell CarcinomaPhase 2NCT07371234
Low-Dose Radiotherapy and Anti-PD-1 Immunotherapy as Neoadjuvant Treatment for Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma
A Phase 2 study testing Neoadjuvant and Adjuvant Immunotherapy, Low-dose radiotherapy and Surgery in people with Locally Advanced Head and Neck Squamous Cell Carcinoma, run by Rui You at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Locally Advanced Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Neoadjuvant and Adjuvant Immunotherapy, Low-dose radiotherapy and Surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteChina
- Study dates
- 15 Dec 2025to 30 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily sign and date the informed consent form.
- Untreated, histologically confirmed squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, or larynx) with CPS ≥1, classified as stage T3-4bN0M0 or T1-4bN1-3M0, corresponding to stage III-IVB according to the AJCC Staging System, 8th Edition.
- Deemed eligible for curative surgery based on surgeon's assessment.
- Age: 18 to 75 years.
- ECOG performance status of 0 or 1.
- Life expectancy greater than 6 months.
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- At least one measurable lesion as per RECIST 1.1 criteria.
- Adequate organ function, defined as meeting all the following criteria (without receipt of blood products, colony-stimulating factors, or hematopoietic growth factors within 14 days prior to testing): Hemoglobin ≥ 90 g/L Absolute neutrophil count ≥ 1.5 × 10⁹/L Platelet count ≥ 100 × 10⁹/L Serum albumin ≥ 28 g/L Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ALT and AST ≤ 2.5 × ULN Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min Activated partial thromboplastin time (aPTT) and international normalized ratio (INR) ≤ 1.5 × ULN (patients on a stable dose of anticoagulant therapy such as low molecular weight heparin or warfarin are eligible if INR is within the therapeutic range) Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels must be evaluated, and patients with normal T3 and T4 levels are eligible.
- Women of childbearing potential must agree to use effective contraception (e.g., intrauterine device, oral contraceptives, or condoms) during the treatment period and for 3 months after the last dose.
- Good compliance with the study protocol.
Who cannot join
- Pregnant or lactating women.
- History of allergy to PD-1 inhibitors.
- History of other malignancies within the past 5 years or at the time of enrollment, with the exception of cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma.
- Uncontrolled cardiac clinical symptoms or diseases, such as: (1) heart failure of NYHA Class II or higher, (2) unstable angina, (3) myocardial infarction within the past year, and (4) patients with clinically significant ventricular or supraventricular arrhythmias requiring intervention.
- Any of the following prior treatments: ① Receipt of any investigational drug prior to the first dose of the current study drug. ② Concurrent participation in another clinical study, unless it is an observational (non-interventional) study or an interventional study during the follow-up phase. ③ Systemic treatment with corticosteroids (>10 mg prednisone daily or equivalent) or other immunosuppressive agents within 2 weeks prior to the first dose of the study drug, with the exception of topical corticosteroid use for local inflammation, prevention of allergic reactions, or management of nausea and vomiting. Inhaled or topical steroids and physiologic replacement doses of corticosteroids (≤10 mg prednisone equivalent daily) are permitted in the absence of active autoimmune disease. ④ Administration of live vaccines within 4 weeks prior to the first dose of the study drug. ⑤ Major surgery or severe trauma within 4 weeks prior to the first dose of the study drug.
- Severe infection (Grade >2 according to Common Terminology Criteria for Adverse Events), such as severe pneumonia, bacteremia, or complicating infections requiring hospitalization, occurring within 4 weeks prior to the first dose of the study drug; or active pulmonary inflammation or signs/symptoms of infection indicated by baseline chest imaging within 2 weeks prior to the first dose, or requiring oral or intravenous antibiotic treatment (excluding prophylactic antibiotics).
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- History of active autoimmune diseases and syndromes (including but not limited to interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism). Patients with vitiligo not requiring intervention in adulthood, or childhood asthma/allergies that have resolved, are not excluded.
- History of immunodeficiency, including HIV positivity, other acquired or congenital immunodeficiency diseases, or history of organ or bone marrow transplantation.
- Patients with active tuberculosis infection based on medical history or CT findings, or a history of active tuberculosis infection within 1 year prior to enrollment, or a history of active tuberculosis infection more than 1 year ago without adequate course of anti-tuberculosis therapy.
- Active hepatitis B (HBV DNA ≥ 2,000 IU/mL or 10,000 copies/mL) or hepatitis C (positive HCV antibody test with HCV RNA above the lower limit of detection).
- Known history of substance abuse, alcohol abuse, or drug use.
- Considered ineligible for participation based on the investigator's judgment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Fifth Affiliated Hospital,Sun Yat-sen University
Guangdong
About this study
Official title: 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)
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.
- Being tested
- Neoadjuvant and Adjuvant Immunotherapy, Low-dose radiotherapy, Surgery, Adjuvant Radiotherapy, Adjuvant Cisplatin
- Keywords
- low-dose radiotherapy, neoadjuvant immunotherapy, Locally Advanced Head and Neck Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant and Adjuvant ImmunotherapyDrug
Neoadjuvant therapy with Toripalimab (240mg, Day 1, Q3W, 2 cycles);Adjuvant immunotherapy with Toripalimab (240mg, Day 1, Q3W, for a total of 15 cycles).
Low-dose radiotherapyRadiation
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).
SurgeryProcedure or surgery
Radical surgery performed 3-4 weeks after neoadjuvant therapy, following a re-evaluation of surgical indications by the surgeon.
Adjuvant RadiotherapyRadiation
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).
Adjuvant CisplatinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Low-Dose RT plus Anti-PD-1 Imunotherapy Arm | Experimental | Patients receive low-dose radiotherapy combined with anti-PD-1 monoclonal antibody immunotherapy as neoadjuvant treatment prior to surgical resection. Receives: Drug: Neoadjuvant and Adjuvant Immunotherapy; Radiation: Low-dose radiotherapy; Procedure: Surgery; Radiation: Adjuvant Radiotherapy; Drug: Adjuvant Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Main pathological response rate
The proportion of patients with residual living tumor cells in the tumor bed under microscopy after HE staining of the specimens organized is less than 10%.
Measured: 1 week post-surgery
Secondary outcomes (10)
Progression-free survival
From random grouping to the time interval until tumor progression or death for any reason, or until the last follow-up time if there is no tumor progression.
Measured: 2 years after enrollment treatment
Pathological complete response rate
The proportion of patients with no residual live tumor cells under the microscope.
Measured: 1 week post-surgery
Objective response rate
Evaluate the proportion of patients with objective response (complete response and partial response) through imaging assessments such as MRI and CT.
Measured: 3-4 weeks after neoadjuvant therapy
Overall survival
The time interval from random grouping to the time of death for any reason, or to the last follow-up time if there is no death.
Measured: 2 years after enrollment treatment
Adverse Events Reporting
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Measured: 1 year
Head and Neck Cancer-Specific Quality of Life
Changes from baseline in head and neck cancer-specific symptoms and functions were assessed using the EORTC QLQ-H\&N35 module (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Cancer Module). The scores range from 0 to 100, with higher scores indicating a better quality of life outcome and lower scores indicating worse symptoms or functions.
Measured: 1 year
Health-related Quality of Life
Changes from baseline in patient-reported quality of life were assessed using the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Version 3.0). The scores range from 0 to 100, with higher scores indicating a better quality of life outcome and lower scores indicating worse symptoms or functions.
Measured: 1 year
Pathological tumor remission rate -2
The proportion of patients with tumor necrosis under a microscope, where the ratio of keratin fragments and giant cells/tissue cells in tissue sections is not less than 50%.
Measured: 1 week post-surgery
Non-surgical delay rate
The proportion of patients whose surgical time is more than 4 weeks longer than planned.
Measured: 8 weeks after two cycles of neoadjuvant therapy
R0 resection rate
The proportion of patients who achieved R0 resection (where the tumor is completely excised during surgery and the margin tissue pathology is negative) among all patients who underwent surgical resection.
Measured: 1 week post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2026
- Study start15 Dec 2025
- Primary completion15 Jan 2027 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rui You
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Rui You, Fifth Affiliated Hospital, Sun Yat-Sen University
- Investigators
- Rui You, Study director, Fifth Affiliated Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07371234
- Sponsor's protocol ID
- ZDWY.FSZLK.011
- Status last verified
- Jan 2026
- First submitted
- 19 Jan 2026
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT07371234
- Acronym / sponsor ID
- ZDWY.FSZLK.011
- Keywords
- low-dose radiotherapy, neoadjuvant immunotherapy, Locally Advanced Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Rui YouUniversity, hospital or other
- Study start
- 15 Dec 2025 (actual)
- Primary completion
- 15 Jan 2027 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 27 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Low-Dose RT plus Anti-PD-1 Imunotherapy Arm | Experimental | Drug: Neoadjuvant and Adjuvant Immunotherapy, Radiation: Low-dose radiotherapy, Procedure: Surgery, Radiation: Adjuvant Radiotherapy, Drug: Adjuvant CisplatinPatients receive low-dose radiotherapy combined with anti-PD-1 monoclonal antibody immunotherapy as neoadjuvant treatment prior to surgical resection. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Voluntarily sign and date the informed consent form.
- Untreated, histologically confirmed squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, or larynx) with CPS ≥1, classified as stage T3-4bN0M0 or T1-4bN1-3M0, corresponding to stage III-IVB according to the AJCC Staging System, 8th Edition.
- Deemed eligible for curative surgery based on surgeon's assessment.
- Age: 18 to 75 years.
- ECOG performance status of 0 or 1.
Key exclusion criteria (12 listed)
- Pregnant or lactating women.
- History of allergy to PD-1 inhibitors.
- History of other malignancies within the past 5 years or at the time of enrollment, with the exception of cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma.
- Uncontrolled cardiac clinical symptoms or diseases, such as: (1) heart failure of NYHA Class II or higher, (2) unstable angina, (3) myocardial infarction within the past year, and (4) patients with clinically significant ventricular or supraventricular arrhythmias requiring intervention.
- Any of the following prior treatments: ① Receipt of any investigational drug prior to the first dose of the current study drug. ② Concurrent participation in another clinical study, unless it is an observational (non-interventional) study or an interventional study during the follow-up phase. ③ Systemic treatment with corticosteroids (>10 mg prednisone daily or equivalent) or other immunosuppressive agents within 2 weeks prior to the first dose of the study drug, with the exception of topical corticosteroid use for local inflammation, prevention of allergic reactions, or management of nausea and vomiting. Inhaled or topical steroids and physiologic replacement doses of corticosteroids (≤10 mg prednisone equivalent daily) are permitted in the absence of active autoimmune disease. ④ Administration of live vaccines within 4 weeks prior to the first dose of the study drug. ⑤ Major surgery or severe trauma within 4 weeks prior to the first dose of the study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neoadjuvant and Adjuvant ImmunotherapyNeoadjuvant therapy with Toripalimab (240mg, Day 1, Q3W, 2 cycles);Adjuvant immunotherapy with Toripalimab (240mg, Day 1, Q3W, for a total of 15 cycles). | Drug | Low-Dose RT plus Anti-PD-1 Imunotherapy Arm |
| Low-dose radiotherapyLow-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). | Radiation | Low-Dose RT plus Anti-PD-1 Imunotherapy Arm |
| SurgeryRadical surgery performed 3-4 weeks after neoadjuvant therapy, following a re-evaluation of surgical indications by the surgeon. | Procedure or surgery | Low-Dose RT plus Anti-PD-1 Imunotherapy Arm |
| Adjuvant RadiotherapyLow-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). | Radiation | Low-Dose RT plus Anti-PD-1 Imunotherapy Arm |
| Adjuvant CisplatinHigh-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. | Drug | Low-Dose RT plus Anti-PD-1 Imunotherapy Arm |
Primary outcome
Main pathological response rate
Time frame: 1 week post-surgery
The proportion of patients with residual living tumor cells in the tumor bed under microscopy after HE staining of the specimens organized is less than 10%.
10 secondary outcomes
Progression-free survival
Time frame: 2 years after enrollment treatment
Pathological complete response rate
Time frame: 1 week post-surgery
Objective response rate
Time frame: 3-4 weeks after neoadjuvant therapy
Overall survival
Time frame: 2 years after enrollment treatment
Adverse Events Reporting
Time frame: 1 year
Head and Neck Cancer-Specific Quality of Life
Time frame: 1 year
Health-related Quality of Life
Time frame: 1 year
Pathological tumor remission rate -2
Time frame: 1 week post-surgery
Non-surgical delay rate
Time frame: 8 weeks after two cycles of neoadjuvant therapy
R0 resection rate
Time frame: 1 week post-surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rui You study director
Fifth Affiliated Hospital, Sun Yat-Sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neoadjuvant and Adjuvant Immunotherapy, Low-dose radiotherapy and Surgery in people with Locally Advanced Head and Neck Squamous Cell Carcinoma, run by Rui You at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xiaoting Cai, MD (86-15602268126, caixiaoting17@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Main pathological response rate (time frame: 1 week post-surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.