head and neck cancer
Conditions
Interventions
Dose Escalation Phase 1 Group:Oncolytic HSV virus 10^6 pfu/mL, 1-4 mL, injected twice with a 2-week interval between doses
Dose Escalation Phase 2 Group:Oncolytic HSV virus 10^8 pfu/mL, 1-4 mL, injected twice with a 2-week interval between doses
Phase Ib Fixed Dose Group:Tislelizumab 200 mg, intravenous infusion on day 1 of each week, every 3 weeks for 2 cycles
Afatinib maleate tablets 30 mg, oral, once daily for 6 consecutive weeks
Oncolytic HSV virus (maximum tolerated dose determined in Phase Ia, injected twice per patient with a 2-week interval between doses, with dosage determined by lymph node size: 1 mL for diameter 2.5 cm
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Age >=18 and <=70 years old, regardless of gender 2. Patients with head and neck squamous carcinoma who are pathologically confirmed and fulfill the following conditions: Patients with locally advanced head and neck squamous carcinoma (excluding nasopharyngeal, salivary gland and thyroid malignant tumors) who are initially diagnosed and have no distant metastasis 3. Non oropharyngeal HNSCC carcinoma and HPV-negative oropharyngeal carcinoma, stages III, IVA and IVB 4. HPV-positive oropharyngeal cancers, stages II and III 5. HPV status of oropharyngeal cancer will be determined by p16 immunohistochemistry. Treatable by surgical resection as evaluated by head and neck surgery 6. Definite lymph node metastasis and lymph node stage is not N0 or Nx. An Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 1 7. Have adequate organ and bone marrow function as defined below: Subjects voluntarily enrolled in the study, signed an informed consent form, and were able to comply with the visits and related procedures specified in the protocol.
Exclusion criteria
Exclusion criteria: 1. Lymph node staging of N0 or Nx status; 2. History of other malignancies (except history of cured and non-recurrent basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical cancer in situ, intramucosal carcinoma of the gastrointestinal tract, and other malignancies considered by the investigator to be eligible for enrollment); 3. Any active autoimmune disease or history of autoimmune disease including, but not limited to, immune-related neurological disorders, multiple sclerosis, autoimmune (demyelinating) neuropathies, Guillain-Barre Syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal Necrolytic Elastosis (TEN) or Stevens-Johnson Syndrome (except for type I diabetes on stabilized doses of insulin); 4. A history of anaphylaxis, severe drug allergy, known allergy to any component of a large protein preparation, PD-1 monoclonal antibody injection, or afatinib prescription (Note: severe allergy is defined as resulting in hospitalization); 5. Received any of the following treatments: (1) Patients with prior use of PD-1 antibody, PD-L1 antibody, CTLA-4 antibody, EGFR antibody, or EGFR-TKI; (2) Patients who have received an anti-tumor vaccine; (3) Use of any active vaccine against infectious diseases (e.g., influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to the first dose or scheduled to be used during the study period; (4) Major surgery or severe trauma within 4 weeks prior to the first dose of study drug; 6. Inhaled or topical steroids and adrenal hormones (>10 mg/day of prednisone) are permitted as an alternative therapy for patients requiring systemic therapy with corticosteroids (>10 mg/day of prednisone) or other immunosuppressive agents within 14 days prior to administration of study drug; 7. Those with serious medical conditions such as abnormal class II or higher cardiac function (NYHA criteria), ischemic heart disease (e.g., myocardial infarction or angina pectoris), clinically significant supraventricular or ventricular arrhythmia with echocardiographic ejection fraction 450 msec in men and >470 msec in women; and an abnormal electrocardiogram that, in the opinion of the investigator, poses an experimental drug There is an additional risk; 8. Subjects with a known history of interstitial pneumonia, history of non-infectious pneumonia, or a high suspicion of interstitial pneumonia; or subjects who may interfere with the detection or management of suspected drug-related pulmonary toxicity; subjects with a prior history of pharmacogenetic or radiologic non-infectious pneumonia that is asymptomatic are permitted to enroll in the study; subjects with active tuberculosis, or with a history of prior tuberculosis infection that has not been controlled with treatment; 9. Patients with hyperthyroidism and patients with organic thyroid disease are not eligible for enrollment; hypothyroidism treated with a stable dose of thyroid replacement hormone is eligible for enrollment, and hypothyroidism that can be controlled with thyroid replacement hormone treatment is eligible for enrollment (control or not will be confirmed by the investigator and/or the endocrinology department); 10. Presence of an active infection, or fever of unknown origin during screening, 48 h prior to the first dose, or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose-Limiting Toxicity (DLT); | — |
Secondary
| Measure | Time frame |
|---|---|
| Major Pathological Response Rate (MPR);Pathological Complete Response Rate (pCR);The Time to first response for the first confirmation of complete response (CR) and partial response (PR);Duration of Response (DOR);Time to First Confirmed Stable Disease;Progression-Free Survival (PFS);Overall Survival (OS);Quality of Life (QOL); | — |
Countries
China
Contacts
Public ContactPeng Xingchen
West China Hospital of Sichuan University
Outcome results
None listed