GV20-0251 and Sintilimab for Neoadjuvant Treatment of Resectable Head and Neck Squamous Cell Carcinoma: A Single-Arm Study
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-70
SponsorWest China Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age 18 to 70 years, inclusive, at the time of signing informed consent; male or female;
Hematologic function:Absolute neutrophil count (ANC) ≥1.5 × 10^9/L;Platelet count (PLT) ≥80 × 10^9/L;Hemoglobin ≥8 g/dL.
Hepatic function:Aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN);Alanine aminotransferase (ALT) ≤2.5 × ULN;Total bilirubin (TBIL) ≤1.5 × ULN;
Serum albumin ≥2.8 g/dL;
Disqualifiers
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;
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;
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;
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;
Trial design
Design model
Sequential
Treatments tested in this trial
GV20-0251
DrugGV20-0251 administered by intravenous infusion on a protocol-specified schedule as part of neoadjuvant treatment prior to surgery.
Sintilimab
DrugSintilimab (PD-1 inhibitor) administered as neoadjuvant therapy in combination with GV20-0251 prior to planned surgery, according to the study protocol.
Treatment groups
9 Participants
are divided into 2 treatment groupsGroup A: GV20-0251 (Dose Level 1) + SintilimabExperimental treatment 2 interventions
Group B: GV20-0251 (Dose Level 2) + SintilimabExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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).
Time frame
From first dose through the end of the DLT assessment window (21 days)Secondary outcomes
1
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).
Time frame
At the time of surgery, after completion of neoadjuvant treatment2
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.
Time frame
At the time of surgery, after completion of neoadjuvant treatment3
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.
Time frame
From baseline to pre-operative tumor assessment following 2 cycles of neoadjuvant therapy (up to 9 weeks).4
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.
Time frame
From first dose through 30 days after the last dose of neoadjuvant treatmentSponsors and contacts
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Source ClinicalTrials.gov