GV20-0251 with sintilimab given before surgery for resectable head and neck cancer

GV20-0251 Combined With Sintilimab for Neoadjuvant Treatment of Resectable Head and Neck Squamous Cell Carcinoma: A Prospective, Single-Arm Clinical Study

This treatment combination will be given before surgery to test safety and early anti-tumor activity in adults with resectable, locally advanced head and neck squamous cell carcinoma.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: West China Hospital (other)
• Drugs / interventions: radiation, prednisone, sintilimab
• Locations: 1 site (Chengdu)
• Trial ID: NCT07457281 on ClinicalTrials.gov

What this trial studies

This single-arm Phase 1 study gives two 3-week cycles of GV20-0251 (10 or 20 mg/kg) combined with fixed-dose sintilimab 200 mg intravenously on Day 1 of each cycle prior to planned surgical resection. A 3+3 dose-escalation design is used to identify dose-limiting toxicities during the neoadjuvant phase, with adverse events graded per CTCAE v5.0 and routine laboratory and clinical monitoring. The main efficacy endpoint is major pathologic response (MPR) in the resected specimen after neoadjuvant therapy, and participants proceed to definitive surgery per protocol. The study is conducted at West China Hospital, Sichuan University with close perioperative safety monitoring.

Who should consider this trial

Good fit: Adults 18–70 with newly diagnosed, resectable locally advanced head and neck squamous cell carcinoma (ECOG 0–1), adequate organ and marrow function, and no distant metastases are the intended participants.

Not a fit: Patients with unresectable or metastatic disease, poor performance status, inadequate organ or marrow function, or cancers excluded by the protocol (for example nasopharyngeal, salivary gland, or thyroid malignancies) are unlikely to benefit from this neoadjuvant combination.

Why it matters

Potential benefit: If successful, this approach could shrink tumors before surgery and potentially improve surgical outcomes and longer-term disease control.

How similar studies have performed: Neoadjuvant PD-1 blockade has shown promising major pathologic response rates in head and neck cancer, but the specific combination of GV20-0251 with sintilimab is novel and not yet established.

Eligibility criteria

Inclusion Criteria:

1. Age 18 to 70 years, inclusive, at the time of signing informed consent; male or female;
2. Histologically confirmed head and neck squamous cell carcinoma (HNSCC) meeting all of the following conditions:

1). Newly diagnosed, locally advanced HNSCC without distant metastasis (excluding nasopharyngeal, salivary gland, and thyroid malignancies): Non-oropharyngeal HNSCC and HPV-negative oropharyngeal cancer: Stage III, IVA, or IVB;HPV-positive oropharyngeal cancer: Stage II or III；HPV status for oropharyngeal cancer will be determined by p16 immunohistochemistry; 2). Assessed by the head and neck surgeon as resectable and amenable to surgical treatment; 3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 4.Adequate organ and bone marrow function, defined as follows:

1. Hematologic function:Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L;Platelet count (PLT) ≥80 × 10\^9/L;Hemoglobin ≥8 g/dL.
2. Hepatic function:Aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN);Alanine aminotransferase (ALT) ≤2.5 × ULN;Total bilirubin (TBIL) ≤1.5 × ULN;
3. Serum albumin ≥2.8 g/dL;
4. Renal function:Serum creatinine ≤1.5 × ULN, orCreatinine clearance (CrCl) \>60 mL/min;
5. Coagulation function:International normalized ratio (INR) ≤1.5;Activated partial thromboplastin time (APTT) ≤1.5 × ULN; 5.Participants must voluntarily agree to participate in the study, sign the informed consent form, and be able to comply with protocol-required visits and study procedures.

Exclusion Criteria:

1. History of other malignancies, except for malignancies considered eligible by the investigator, such as adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or intramucosal gastrointestinal carcinoma that has been cured and has not recurred within 5 years;
2. Active autoimmune disease or history of autoimmune disease, including but not limited to immune-related neurologic disorders, multiple sclerosis, autoimmune demyelinating neuropathy, Guillain-Barré syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome; participants with type 1 diabetes mellitus controlled with a stable dose of insulin may be enrolled;
3. Allergic disease, severe drug allergy history, or known hypersensitivity to macromolecular protein preparations or any component of PD-1 monoclonal antibody injection; severe hypersensitivity is defined as Grade 3 or higher according to CTCAE;
4. Prior receipt of any of the following treatments: 1) prior treatment with PD-1 antibody, PD-L1 antibody, CTLA-4 antibody, EGFR antibody, or EGFR tyrosine kinase inhibitor; 2) prior receipt of any antitumor vaccine; 3) receipt of any live vaccine for prevention of infectious disease within 4 weeks before first dose or planned use during the study, such as influenza vaccine or varicella vaccine; 4) major surgery or severe trauma within 4 weeks before first dose;
5. Requirement for systemic corticosteroid therapy (\>10 mg/day prednisone or equivalent) or other immunosuppressive therapy within 14 days before study drug administration; inhaled or topical corticosteroids and physiologic replacement doses of adrenal steroids are permitted;
6. Severe medical disease, including New York Heart Association (NYHA) Class II or higher cardiac dysfunction, ischemic heart disease such as myocardial infarction or angina pectoris, clinically significant supraventricular or ventricular arrhythmias, left ventricular ejection fraction \<50% by echocardiography, QTc interval \>450 msec in men or \>470 msec in women, or any electrocardiographic abnormality considered by the investigator to pose additional risk with the study drug;
7. Known history of interstitial lung disease, noninfectious pneumonitis, or high suspicion of interstitial lung disease, or any condition that may interfere with the detection or management of suspected drug-related pulmonary toxicity; participants with a prior history of drug-induced or radiation-induced noninfectious pneumonitis who are currently asymptomatic may be enrolled; active tuberculosis, or previous tuberculosis infection that remains uncontrolled after treatment;
8. Hyperthyroidism or organic thyroid disease; participants with hypothyroidism controlled with thyroid hormone replacement therapy may be enrolled if considered adequately controlled by the investigator and/or endocrinologist;
9. Active infection, unexplained fever during screening or within 48 hours before first dose, or use of systemic antibiotics within 1 week before signing informed consent;
10. Active hepatitis B infection (HBV DNA ≥2000 IU/mL or 10\^4 copies/mL), active hepatitis C infection (positive HCV antibody with HCV RNA above the lower limit of detection of the assay), known positive history of human immunodeficiency virus (HIV) infection, or known acquired immunodeficiency syndrome (AIDS);
11. Definite history of neurologic or psychiatric disorders, such as epilepsy or dementia;
12. Known history of drug abuse or alcohol abuse within 3 months before enrollment;
13. Pregnancy or lactation; intention to conceive during treatment or within 4 months after the last dose in the participant or the participant's partner, unprotected sexual activity without contraception, or unwillingness to use adequate contraceptive measures such as condoms, intrauterine devices, or partner sterilization;
14. Receipt of any investigational drug within 4 weeks before first use of study drug, or concurrent participation in another clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study;
15. Any other condition that, in the opinion of the investigator, may interfere with study participation, completion of study treatment, or follow-up.

Where this trial is running

Chengdu

• West China Hospital, Sichuan University — Chengdu, China (RECRUITING)

Study contacts

• Principal investigator: Xingchen Peng, MD — West China Hospital
• Study coordinator: Huaju yang

Conditions: Head and Neck Squamous Cell Carcinoma HNSCC