Sintilimab Plus Chemotherapy as Neoadjuvant and Adjuvant Treatment for Locally Advanced Oral Squamous Cell Carcinoma

NCT07371611 | Recruiting Phase 3

• 1 other identifier: SYSKY-2025-966-01
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label, randomized phase III clinical trial evaluating perioperative treatment with sintilimab combined with chemotherapy in patients with locally advanced oral squamous cell carcinoma. Despite standard treatment with surgery followed by postoperative radiotherapy or chemoradiotherapy, patients with locally advanced oral squamous cell carcinoma remain at high risk of recurrence or metastasis. Recent evidence, including results from the KEYNOTE-689 study, suggests that perioperative immunotherapy may improve survival outcomes, and this approach has been incorporated into NCCN guidelines. Combining immunotherapy with chemotherapy may further improve prognosis in this patient population. Eligible participants will be randomly assigned to either an experimental group or a control group. The experimental group will receive neoadjuvant sintilimab combined with chemotherapy followed by surgery and postoperative treatment based on pathological response. Patients with major pathological response (MPR) will receive adjuvant sintilimab, while patients without MPR will receive postoperative radiotherapy or concurrent chemoradiotherapy combined with sintilimab. The control group will receive standard treatment consisting of surgery followed by postoperative radiotherapy or chemoradiotherapy as clinically indicated. The primary objective of the study is to compare event-free survival between the two groups. Secondary objectives include overall survival, pathological response, safety, and treatment-related adverse events. The results of this study may help optimize perioperative treatment strategies and improve outcomes for patients with locally advanced oral squamous cell carcinoma.

Conditions

Locally Advanced Oral Squamous Cell Carcinoma; Oral Squamous Cell Carcinoma (OSCC)

Keywords

Oral Squamous Cell Carcinoma; Locally Advanced; Sintilimab; Perioperative Immunotherapy; Neoadjuvant Therapy; Adjuvant Therapy; Randomized Phase III Trial

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS)

  Event-free survival is defined as the time from randomization to the first occurrence of disease progression, local or distant recurrence, second primary malignancy, or death from any cause, whichever occurs first.

  2 years

Secondary Outcomes (5)

• overall survival（OS）

  2 years and 5 years.

• pathological complete response（pCR）

  At the time of definitive surgery

• Major Pathological Response (MPR)

  At the time of definitive surgery

• Treatment-related adverse events（TRAE）

  through study completion, an average of 1 year

• Radiologic assessments

  Baseline and preoperative

Study Arms (2)

Experimental arm

EXPERIMENTAL

Neoadjuvant sintilimab combined with TP regimen followed by radical surgery and risk-stratified adjuvant therapy (low-risk: sintilimab monotherapy; high-risk: radiotherapy or concurrent chemoradiotherapy followed by sequential sintilimab).

Drug: Sintilimab plus nab-paclitaxel and platinum-based chemotherapy

Control arm

ACTIVE COMPARATOR

Radical surgery combined with radiotherapy or chemoradiotherapy

Procedure: Radical surgery combined with radiotherapy or chemoradiotherapy

Interventions

Radical surgery combined with radiotherapy or chemoradiotherapy PROCEDURE

Participants undergo radical surgical resection as primary treatment, followed by postoperative radiotherapy or concurrent chemoradiotherapy according to pathological risk factors and standard clinical practice.

Also known as: surgery, radiotherapy, chemoradiotherapy

Control arm

Sintilimab plus nab-paclitaxel and platinum-based chemotherapy DRUG

Neoadjuvant sintilimab combined with TP regimen followed by radical surgery and risk-stratified adjuvant therapy (low-risk: sintilimab monotherapy; high-risk: radiotherapy or concurrent chemoradiotherapy followed by sequential sintilimab).

Also known as: Sintilimab, Nab-paclitaxel, Carboplatin, Cisplatin

Experimental arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years at the time of enrollment.
• ECOG Performance Status (PS) score of 0-1.
• Primary lesion pathologically confirmed as oral squamous cell carcinoma (OSCC), including tumors of the anterior two-thirds of the tongue, gingiva, buccal mucosa, floor of the mouth, hard palate, or retromolar trigone.
• Clinical stage III or IVA, defined as T1-2 with N1-2, or T3-4a and/or N0-2, according to the AJCC 8th edition OSCC TNM staging system.
• Willingness to undergo surgical treatment.
• Presence of at least one measurable lesion as defined by RECIST v1.1 criteria.
• Voluntary participation with full understanding and signing of the informed consent form, and willingness to comply with study procedures.
• Adequate major organ function, meeting all of the following laboratory criteria:
• \. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L without granulocyte colony-stimulating factor (G-CSF) administration within 14 days prior to testing.
• \. Platelet count ≥ 100 × 10⁹/L without blood transfusion within the previous 14 days.
• \. Hemoglobin \> 90 g/L without blood transfusion or erythropoietin use within the previous 14 days.
• \. Total bilirubin ≤ 1.5 × the upper limit of normal (ULN); ≤ 3 × ULN in cases of Gilbert's syndrome or non-hepatic indirect bilirubin elevation.
• \. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; ≤ 5 × ULN for patients with hepatic involvement.
• \. Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by the Cockcroft-Gault formula) ≥ 60 mL/min.
• \. Adequate coagulation function, defined as INR or prothrombin time (PT) ≤ 1.5 × ULN.

You may not qualify if:

• Prior treatment targeting PD-1, PD-L1, PD-L2, or CTLA-4, or other therapies targeting T-cell costimulatory or immune checkpoint pathways.
• Participation in another interventional clinical trial or use of an investigational drug or device within 4 weeks prior to the first dose.
• History of radiotherapy involving the head, neck, or maxillofacial regions.
• Use of traditional Chinese medicines or immunomodulatory agents with OSCC indications (e.g., thymosin, interferon, interleukin) within 2 weeks before first dosing; local therapy for pleural effusion control is permitted.
• History of active autoimmune disease within the past 2 years requiring systemic therapy (e.g., corticosteroids or immunosuppressants). Exceptions include:
• \. Hypothyroidism controlled with thyroid hormone replacement therapy.
• \. Diabetes mellitus controlled with insulin.
• \. Adrenal or pituitary insufficiency treated with physiologic doses of corticosteroids.
• Use of immunosuppressive agents:
• \. Systemic corticosteroid therapy within 1 week prior to the first dose is prohibited.
• \. Use of other immunosuppressive drugs is prohibited.
• \. Intranasal, inhaled, or topical corticosteroids are permitted.
• \. Physiologic doses of corticosteroids (e.g., prednisone ≤10 mg/day or equivalent) are permitted.
• Prior systemic antitumor therapy, except patients who have had ≥12 months of treatment-free interval between the last chemotherapy and initiation of neoadjuvant therapy.
• Previous allogeneic organ or hematopoietic stem cell transplantation (excluding corneal transplantation).

Sponsors & Collaborators

• Qunxing Li,MD: lead

Study Sites (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510123, China

RECRUITING

Related Publications (1)

• Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, Chernock R, Tahara M, Harrington KJ, Klochikhin AL, Brana I, Vasconcelos Alves G, Hughes BGM, Oliva M, Pinto Figueiredo Lima I, Ueda T, Rutkowski T, Schroeder U, Mauz PS, Fuereder T, Laban S, Oridate N, Popovtzer A, Mach N, Korobko Y, Costa DA, Hooda-Nehra A, Rodriguez CP, Bell RB, Manschot C, Benjamin K, Gumuscu B, Adkins D; KEYNOTE-689 Investigators. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med. 2025 Jul 3;393(1):37-50. doi: 10.1056/NEJMoa2415434. Epub 2025 Jun 18.

  PMID: 40532178 RESULT

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

sintilimab; 130-nm albumin-bound paclitaxel; Platinum Compounds; Carboplatin; Cisplatin; Radiotherapy; Chemoradiotherapy; Surgical Procedures, Operative

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)

Inorganic Chemicals; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Nitrogen Compounds; Therapeutics; Combined Modality Therapy; Drug Therapy

Study Officials

• Jinsong Li, MD, PhD

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liansheng Wang, PhD (Candidate)

CONTACT

+8613535330603; wanglsh25@mail2.sysu.edu.cn

Qunxing Li, MD, PhD

CONTACT

86+18320699771; liqx73@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study. No masking is applied.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: December 26, 2025
• First Posted: January 28, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2033
• Last Updated: January 28, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)