HPV-positive oropharyngeal squamous cell carcinoma
Conditions
Interventions
High-dose group:WSK-IM05 (1.6×10^11 vp) +Tislelizumab
Low-dose group:WSK-IM05 (4×10^10 vp) +Tislelizumab
Middle-dose group:WSK-IM05 (8×10^10 vp) +Tislelizumab
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years, male or female; 2. Histologically conffrmed oropharyngeal squamous cell carcinoma meeting all of the following criteria: (1) Newly diagnosed, HPV-positive, without distant metastases; (2) Conffrmed p16 positive by immunohistochemistry (deffned as =70% moderate to strong nuclear and cytoplasmic staining of tumor cells); (3) Assessed by head and neck surgery as resectable; (4) 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) >= 1.5x10^9/L; platelet count (PLT) >= 80x10^9/L; hemoglobin >= 8 g/dL; Liver function: AST, ALT, ALP = 2.8 g/dL.Renal function: serum creatinine (Cr) 60 mL/min; Coagulation: international normalized ratio (INR) <= 1.5; activated partial thromboplastin time (APTT) <= 1.5xULN; 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
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, superffcial 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, inffammatory 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 deffned as requiring hospitalization); 4. Prior receipt of any of the following treatments: (1) Prioruse of PD-1 antibody, PD-L1 antibody, PD-L2 antibody, CTLA-4 antibody, EGFR antibody, or EGFR-TKI; (2) Prior receipt of an antitumor vaccine; (3) Use of any active vaccine against infectious diseases (e.g., inffuenza vaccine, varicella vaccine) within 4 weeks before ffrst dose or planned during the study period; (4) Major surgery or severe trauma within 4 weeks before ffrst dose; (5) Prior antitumor toxicity notrecovered to = 10 mmol/L); Poorly controlled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg); Echocardiography showing ejection fraction 450 msec in males, > 470 msec in females; Any ECG abnormality that, in the investigator’s opinion, poses additional risk for the study drug; 6. History of interstitial lung disease, non-infectious pneumonitis, or high suspicion of interstitial lung disease; or conditions that might interfere with detection or management of suspected drug-related pulmonary toxicity. Patients with a prior history of drug-induced or radiation-induced non-infectious pneumonitis who are asymptomatic may be enrolled. Active tuberculosis or past tuberculosis that remains uncontrolled aftertreatment; 7. Patients with hyperthyroidism or organic thyroid disease. Hypothyroidism managed with astable dose of thyroid replacement hormone may be enrolled (as conffrmed by the investigator and/or endocrinologist); 8. Active infection, or unexplained fever within 48 hours before ffrst dose, or use ofsystemic antibiotics within 1 week before signing informed consent; 9. Active hepatitis B (HBV DNA >=2000 IU/mL or 104 copies/mL) or active hepatitis C (positive HCV antibody with HCV RNA above thelower limit of detection), or known positive HIV test or known acquired immunodeffciency syndrome(AIDS); 10. Clear history of neurological or psychi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of serious adverse events (SAEs);Incidence of dose-limiting toxicity (DLT);Incidence and severity of treatment-related adverse events (TRAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| HPV titer (viral load) in blood/saliva;HPV16 E6/E7 Tetramer+ CD8+ T cell frequency;Tumor PD-L1 expression, TMB, and changes in the immune microenvironment;Proportion of TNF-a+/IFN-?+ CD8+ T cells;Event-free survival (EFS);Objective response rate (ORR);Anti-HPV16 E6/E7 antibody levels;Pathologic complete response rate (pCR);Major pathologic response rate (MPR); | — |
Countries
China
Contacts
Public ContactXingchen Peng
West China Hospital, Sichuan University
Outcome results
None listed