Sintilimab with chemotherapy before and after surgery for locally advanced oral squamous cell carcinoma

Sintilimab Plus Chemotherapy as Neoadjuvant and Adjuvant Treatment for Locally Advanced Oral Squamous Cell Carcinoma: A Multicenter, Open-label, Randomized, Phase III Clinical Study

This trial will test whether adding sintilimab to chemotherapy before and after surgery helps people with locally advanced oral squamous cell carcinoma have fewer recurrences and better survival.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 104 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: sintilimab, chemotherapy, prednisone, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07371611 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label, randomized phase III trial compares perioperative sintilimab plus chemotherapy versus standard surgery with or without postoperative radiotherapy or chemoradiotherapy in patients with resectable, locally advanced OSCC. Patients randomized to the experimental arm receive neoadjuvant sintilimab combined with nab-paclitaxel and platinum-based chemotherapy followed by radical surgery and risk-adapted adjuvant treatment based on pathological response. The control arm receives upfront surgery followed by standard postoperative radiotherapy or chemoradiotherapy as indicated. Primary endpoints include pathological response and longer-term outcomes such as event-free and overall survival, with safety and tolerability also monitored.

Who should consider this trial

Good fit: Adults aged 18–75 with resectable, clinical stage III–IVA oral squamous cell carcinoma (ECOG 0–1), at least one measurable lesion, adequate organ function, and willingness to undergo surgery and study procedures.

Not a fit: Patients with unresectable or metastatic disease, poor performance status, or significant organ dysfunction are unlikely to benefit from this perioperative approach.

Why it matters

Potential benefit: If successful, adding perioperative sintilimab could lower recurrence rates and improve survival for patients with locally advanced OSCC.

How similar studies have performed: Similar perioperative immunotherapy approaches, including results from KEYNOTE-689 in resectable head and neck cancers, have shown improved event-free survival, though perioperative sintilimab specifically in OSCC is still being tested.

Eligibility criteria

Inclusion Criteria:

* 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:
* 1\. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L without granulocyte colony-stimulating factor (G-CSF) administration within 14 days prior to testing.
* 2\. Platelet count ≥ 100 × 10⁹/L without blood transfusion within the previous 14 days.
* 3\. Hemoglobin \> 90 g/L without blood transfusion or erythropoietin use within the previous 14 days.
* 4\. Total bilirubin ≤ 1.5 × the upper limit of normal (ULN); ≤ 3 × ULN in cases of Gilbert's syndrome or non-hepatic indirect bilirubin elevation.
* 5\. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; ≤ 5 × ULN for patients with hepatic involvement.
* 6\. Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by the Cockcroft-Gault formula) ≥ 60 mL/min.
* 7\. Adequate coagulation function, defined as INR or prothrombin time (PT) ≤ 1.5 × ULN.
* 8\. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. Subjects with abnormal TSH may be enrolled if total T3 (or FT3) and FT4 are within normal limits.
* 9\. Normal myocardial enzyme profile (minor laboratory abnormalities deemed clinically insignificant by the investigator are acceptable).
* 10\. For women of childbearing potential, a negative urine or serum pregnancy test within 3 days prior to the first dose of study treatment (Cycle 1, Day 1) is required. If the urine test is indeterminate, a serum test must be performed. Non-childbearing women are defined as those who have been postmenopausal for at least one year or have undergone surgical sterilization or hysterectomy.
* 11\. All participants (male or female) with reproductive potential must agree to use highly effective contraception (annual failure rate \<1%) during the entire treatment period and for at least 120 days after the last study drug dose or 180 days after the last chemotherapy dose.

Exclusion Criteria:

* 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:
* 1\. Hypothyroidism controlled with thyroid hormone replacement therapy.
* 2\. Diabetes mellitus controlled with insulin.
* 3\. Adrenal or pituitary insufficiency treated with physiologic doses of corticosteroids.
* Use of immunosuppressive agents:
* 1\. Systemic corticosteroid therapy within 1 week prior to the first dose is prohibited.
* 2\. Use of other immunosuppressive drugs is prohibited.
* 3\. Intranasal, inhaled, or topical corticosteroids are permitted.
* 4\. 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).
* Known hypersensitivity to sintilimab, carboplatin, cisplatin, nab-paclitaxel, or any of their excipients.
* Failure to recover to baseline or ≤ grade 1 (except fatigue or alopecia) from adverse events or complications of prior interventions before enrollment.
* Known human immunodeficiency virus (HIV) infection (HIV-1/2 antibody positive).
* Untreated active hepatitis B infection (HBsAg positive with HBV-DNA above the ULN). Subjects meeting the following criteria may be enrolled:
* 1\. HBV viral load \<1000 copies/mL (200 IU/mL) and receiving antiviral therapy during the study to prevent reactivation.
* 2\. Subjects who are anti-HBc(+), HBsAg(-), anti-HBs(-), and HBV-DNA(-) do not require prophylactic antiviral therapy but must be closely monitored for viral reactivation.
* Active hepatitis C infection (HCV antibody positive with HCV-RNA above the lower limit of detection).
* Receipt of a live vaccine within 30 days prior to the first dose (inactivated vaccines, such as inactivated influenza vaccine, are permitted; intranasal live vaccines are not allowed).
* Pregnant or breastfeeding women.
* Presence of severe or uncontrolled systemic diseases, including but not limited to:
* 1\. Cardiac disorders: severe arrhythmias (e.g., complete left bundle branch block, second-degree or higher atrioventricular block, ventricular arrhythmia, or persistent atrial fibrillation), unstable angina, or congestive heart failure (NYHA class ≥ II).
* 2\. Vascular disorders: history of unstable angina, myocardial infarction, transient ischemic attack, or stroke within 6 months before enrollment.
* 3\. Poorly controlled hypertension (systolic BP \>140 mmHg or diastolic BP \>90 mmHg).
* 4\. Pulmonary disorders: noninfectious pneumonitis requiring corticosteroid therapy within 1 year prior to the first dose, or active interstitial lung disease.
* 5\. Infectious diseases: active infections requiring systemic treatment, or severe uncontrolled infections.
* 6\. Active pulmonary tuberculosis.
* 7\. Gastrointestinal disorders: clinically active diverticulitis, intra-abdominal abscess, or intestinal obstruction.
* 8\. Hepatic disorders: liver cirrhosis, decompensated liver disease, or acute/chronic active hepatitis.
* 9\. Poorly controlled diabetes mellitus: fasting blood glucose (FBG) \>10 mmol/L.
* 10\. Renal dysfunction: urine protein ≥++ on urinalysis and 24-hour urinary protein \>1.0 g.
* 11\. Psychiatric disorders: severe mental illness that may affect treatment compliance.
* Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Jinsong Li, MD, PhD — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Liansheng Wang, PhD (Candidate)

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