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

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

The goal of this clinical trial is to learn whether neoadjuvant GV20-0251 combined with sintilimab is safe and tolerable, and to explore its preliminary antitumor activity, in adults with resectable, locally advanced head and neck squamous cell carcinoma at West China Hospital, Sichuan University. The main questions it aims to answer are: What is the incidence of dose-limiting toxicities (DLTs) during neoadjuvant treatment with GV20-0251 in combination with sintilimab in the dose-escalation phase? What is the major pathologic response (MPR) rate in resected specimens after neoadjuvant treatment? Participants will receive two 3-week cycles of neoadjuvant therapy using a 3+3 dose-escalation design (GV20-0251 at 10 mg/kg or 20 mg/kg plus fixed-dose sintilimab 200 mg, both given by intravenous infusion on Day 1 of each cycle), undergo protocol-specified safety monitoring with adverse events graded per CTCAE v5.0 and routine clinical assessments and laboratory tests, proceed to definitive surgery after neoadjuvant therapy, receive postoperative adjuvant therapy, and complete post-treatment safety follow-up and protocol-defined long-term follow-up for disease status and survival outcomes.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma HNSCC
• Intervention / Treatment: Drug: GV20-0251; Drug: Sintilimab

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Huaju Yang; Phone Number: +8613340239461; Email: yhjyanghuaju@163.com

Study Locations

• China
  • Chengdu, China
    • Recruiting
    • West China Hospital, Sichuan University
    • Contact: Huaju Yang; Phone Number: +8613340239461; Email: yhjyanghuaju@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GV20-0251 (Dose Level 1) + Sintilimab; Neoadjuvant treatment: Participants receive GV20-0251 10 mg/kg plus sintilimab by intravenous (IV) infusion on Day 1 of each 21-day cycle for 2 cycles prior to surgery. Adjuvant treatment: Following surgical resection, participants receive sintilimab by IV infusion on Day 1 of each 21-day cycle for 15 cycles, plus investigator's choice of standard-of-care (SOC) treatment consisting of radiotherapy, with or without cisplatin 100 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 3 cycles (up to 9 weeks).	Drug: GV20-0251; GV20-0251 administered by intravenous infusion on a protocol-specified schedule as part of neoadjuvant treatment prior to surgery.; Drug: Sintilimab; Sintilimab (PD-1 inhibitor) administered as neoadjuvant therapy in combination with GV20-0251 prior to planned surgery, according to the study protocol.
Experimental: GV20-0251 (Dose Level 2) + Sintilimab; Neoadjuvant treatment: Participants receive GV20-0251 20 mg/kg plus sintilimab by intravenous (IV) infusion on Day 1 of each 21-day cycle for 2 cycles prior to surgery. Adjuvant treatment: Following surgical resection, participants receive sintilimab by IV infusion on Day 1 of each 21-day cycle for 15 cycles, plus investigator's choice of standard-of-care (SOC) treatment consisting of radiotherapy, with or without cisplatin 100 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 3 cycles (up to 9 weeks).	Drug: GV20-0251; GV20-0251 administered by intravenous infusion on a protocol-specified schedule as part of neoadjuvant treatment prior to surgery.; Drug: Sintilimab; Sintilimab (PD-1 inhibitor) administered as neoadjuvant therapy in combination with GV20-0251 prior to planned surgery, according to the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities (DLTs) of GV20-0251 in combination with sintilimab	The incidence of dose-limiting toxicities (DLTs) of GV20-0251 in combination with sintilimab will be assessed to determine the recommended expansion dose (RDE).	From first dose through the end of the DLT assessment window (21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR) Rate	Among participants who undergo surgery, pathologic complete response (pCR) is defined according to immune-related pathologic response criteria (irPR) as no residual viable tumor cells in the tumor bed or resected lymph nodes (%RVT = 0).	At the time of surgery, after completion of neoadjuvant treatment
Adverse Events (AEs)	Adverse events (AEs) will be assessed according to CTCAE version 5.0, and all treatment-related adverse events will be reported to evaluate the safety of treatment.	From first dose through 30 days after the last dose of neoadjuvant treatment
Event-Free Survival (EFS)	Event-free survival (EFS) is defined as the time from first dose to the first occurrence of any of the following events: disease progression during neoadjuvant treatment that precludes definitive surgery, local, regional, or distant recurrence after surgery, or death from any cause. Participants without an event will be censored at the date of last disease assessment or last follow-up.	From first dose to the first occurrence of an event, assessed up to 2 years
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the proportion of participants with a complete response (CR) or partial response (PR), as assessed according to RECIST version 1.1 and iRECIST.	From baseline to pre-operative tumor assessment following 2 cycles of neoadjuvant therapy (up to 9 weeks).
Major Pathologic Response (MPR) Rate	Among participants who undergo surgery, major pathologic response (MPR) is defined according to immune-related pathologic response criteria (irPRC) as ≤10% residual viable tumor cells in the tumor bed (%RVT ≤10%), regardless of whether residual viable tumor cells are present in lymph nodes.	At the time of surgery, after completion of neoadjuvant treatment

Collaborators and Investigators

• Sponsor: West China Hospital
• Investigators: Principal Investigator: Xingchen Peng, MD, West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: sintilimab
• Other Study ID Numbers: 2025-2551

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No