HPV-positive Oropharyngeal Squamous Cell Carcinoma
Conditions
Keywords
HPV-positive oropharyngeal squamous cell carcinoma, Neoadjuvant therapy, PD-1 inhibitor, Pathological response
Brief summary
This phase I, open-label, single-arm trial uses a "3+3" dose-escalation design to evaluate the safety, tolerability, and preliminary efffcacy of intranasal WSK-IM05 vaccine combined with tislelizumab as neoadjuvant therapy in patients with resectable HPV-positive oropharyngeal squamous cell carcinoma. Participants receive two cycles of WSK-IM05 (intranasal) and tislelizumab (200 mg IV) on day 1 of each 3-week cycle, followed by surgery. After surgery, patients receive standard of care (chemoradiotherapy or radiotherapy as indicated) plus 15 cycles of adjuvant tislelizumab. The main outcomes include dose-limiting toxicities and treatment-related adverse events.
Interventions
BIOLOGICALWSK-IM05 (4×10^10 vp)
Intranasal recombinant adenovirus vaccine WSK-IM05 at a dose of 4×10\^10 vp administered via nasal spray on day 1 of each 3-week cycle for 2 cycles.
BIOLOGICALWSK-IM05 (8×10^10 vp)
Intranasal recombinant adenovirus vaccine WSK-IM05 at a dose of 8×10\^10 vp administered via nasal spray on day 1 of each 3-week cycle for 2 cycles.
BIOLOGICALWSK-IM05 (1.6x10^11 vp)
Intranasal recombinant adenovirus vaccine WSK-IM05 at a dose of 1.6x10\^11 vp administered via nasal spray on day 1 of each 3-week cycle for 2 cycles.
DRUGTislelizumab
Tislelizumab at a dose of 200 mg administered intravenously on day 1 of each 3-week cycle for 2 cycles (neoadjuvant phase), followed by 200 mg intravenously every 3 weeks for 15 cycles (adjuvant phase after surgery).
Sponsors
West China Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Age ≥ 18 years, male or female.2. Histologically confirmed oropharyngeal squamous cell carcinoma meeting all of the following criteria: Newly diagnosed, HPV-positive, without distant metastases; Confirmed p16 positive by immunohistochemistry (defined as ≥70% moderate to strong nuclear and cytoplasmic staining of tumor cells)；Assessed by head and neck surgery as resectable; Willing to undergo surgical treatment.3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.4. Adequate organ and bone marrow function, defined as:Hematology: neutrophil count (NEUT) ≥ 1.5×10⁹/L; platelet count (PLT) ≥ 80×10⁹/L; hemoglobin ≥ 8 g/dL; Liver function: AST, ALT, ALP ≤ 2.5×upper limit of normal (ULN); total bilirubin (TBIL) ≤ 1.5×ULN; Albumin ≥ 2.8 g/dL.Renal function: serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (CCr) \> 60 mL/min; Coagulation: international normalized ratio (INR) ≤ 1.5; activated partial thromboplastin time (APTT) ≤ 1.5×ULN; Adenovirus type 5(Ad5) neutralizing antibody titer ≤ 1:200.5. Willing to voluntarily sign the informed consent form and able to comply with protocol-required visits and procedures.
Exclusion criteria
1\. History of other malignancies (except for adequately treated and with no recurrence within 5 years:basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer,cervical carcinoma in situ, intramucosal gastrointestinal carcinoma, or other malignancies deemed eligible by the investigator).2. Any active autoimmune disease or history of autoimmune disease,including but not limited to immune-related neurological 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 (excluding type I diabetes mellitus managed with stable insulin doses).3. History of allergic disease, severe drug allergy, or known allergy to any component of large molecule protein preparations,PD-1 monoclonal antibody injections, or the intranasal recombinant adenovirus vaccine (note: severe allergy is defined as requiring hospitalization).4. Prior receipt of any of the following treatments:a. Prior use of PD-1 antibody, PD-L1 antibody, PD-L2 antibody, CTLA-4 antibody, EGFR antibody, or EGFR-TKI.b. Prior receipt of an antitumor vaccine.c. Use of any active vaccine against infectious diseases (e.g.,inffuenza vaccine, varicella vaccine) within 4 weeks before first dose or planned during the study period.d. Major surgery or severe trauma within 4 weeks before first dose.e. Prior antitumor toxicity not recovered to ≤ CTCAE v5.0 grade 1 (excluding alopecia or sequelae of prior platinum-related neuropathy) or to the levels specified in inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | First 21 days after first dose of WSK-IM05 | Proportion of participants experiencing DLTs within the DLT observation period (first 21 days after the first dose), as defined per protocol. |
| Incidence and Severity of Treatment-Related Adverse Events (TRAEs) | From first dose through 30 days after last dose of WSK-IM05 | Type, incidence, severity (grade 1-5 according to CTCAE v5.0), and causality assessment of all treatment-related adverse events. |
| Incidence of Serious Adverse Events (SAEs) | From first dose through 30 days after last dose | Including immune-related adverse events (irAEs), injection/administration site reactions, allergic reactions, etc. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response (MPR) | At time of surgery (approx. Week 6-10) | Proportion of participants who undergo surgery with residual viable tumor ≤10% (%RVT ≤10%) in the tumor bed according to irPRC criteria, regardless of lymph node status. |
| Pathological Complete Response (pCR) | At time of surgery (approx. Week 6-10) | Proportion of participants who undergo surgery with no residual viable tumor cells (%RVT = 0) in the tumor bed and resected lymph nodes according to irPRC criteria. |
| Objective Response Rate (ORR) | After 2 cycles of neoadjuvant therapy (prior to surgery, approx. Week 5-9) | Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria. |
| Event-Free Survival (EFS) | From first dose up to approximately 3 years | Time from first dose to first occurrence of any of the following: disease progression during neoadjuvant therapy leading tolerability to undergo radical surgery; local, regional, or distant tumor recurrence after surgery; or death from any cause. |
Countries
China
Contacts
CONTACTXingchen Peng
Outcome results
None listed