A Prospective, Single-arm Clinical Study of Immune-targeted Therapy Combined With Lysogenic HSV Virus for the Neoadjuvant Treatment of Surgically Resectable Head and Neck Squamous Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Lysogenic HSV virus.
- Conditions
- HNSCC
- Sponsor
- West China Hospital
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- The incidence of dose-limiting toxicity (DLT) Incidence.
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Evaluation of the safety and tolerability of immune-targeted therapy combined with neoadjuvant therapy with lysogenic HSV virus for patients with surgically resectable squamous carcinoma of the head and neck.
Detailed Description
Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignant tumors in the head and neck region. Globally, both its incidence and mortality rates have shown a significant upward trend, posing a serious threat to the life and health of patients. Although surgical resection is the main treatment approach for resectable HNSCC, a considerable number of patients still face a high risk of local recurrence and distant metastasis after surgery, which are the key factors contributing to poor prognosis. In recent years, immune-targeted therapy has emerged in the field of malignant tumor treatment and demonstrated unique treatment advantages and potential. It can specifically act on relevant targets of tumor cells, precisely regulate the body's immune system, and effectively enhance the body's immune response to tumor cells, thereby inhibiting the malignant biological behaviors of tumor cells such as growth, proliferation, and metastasis. Oncolytic herpes simplex virus (HSV) has the ability to specifically replicate within tumor cells and lyse them. Meanwhile, it can also induce a strong anti-tumor immune response in the body and has broad application prospects in tumor treatment. Based on the above situation, this study innovatively proposes to combine immune-targeted therapy with oncolytic HSV virus for the neoadjuvant treatment of resectable HNSCC. The aim is to fully utilize the synergistic effect of the two treatment modalities, minimize the tumor volume to the greatest extent, reduce the tumor stage, improve the surgical resection rate and radicality, decrease the risks of postoperative recurrence and metastasis, and ultimately improve the quality of life and prognosis of patients. By conducting this prospective, single-arm clinical study, it is expected to provide a more efficient, safe, and innovative treatment strategy and clinical practice basis for the treatment of resectable HNSCC.
Investigators
Xingchen Peng
PhD, Professor
West China Hospital
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 and ≤70 years old, regardless of gender;
- •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;
- •Non oropharyngeal HNSCC carcinoma and HPV-negative oropharyngeal carcinoma, stages III, IVA and IVB;
- •HPV-positive oropharyngeal cancers, stages II and III;
- •HPV status of oropharyngeal cancer will be determined by p16 immunohistochemistry.
- •Treatable by surgical resection as evaluated by head and neck surgery;
- •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;
- •Have adequate organ and bone marrow function as defined below:
Exclusion Criteria
- •Lymph node staging of N0 or Nx status;
- •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);
- •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);
- •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);
- •Received any of the following treatments:
- •Patients with prior use of PD-1 antibody, PD-L1 antibody, CTLA-4 antibody, EGFR antibody, or EGFR-TKI;
- •Patients who have received an anti-tumor vaccine;
- •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;
- •Major surgery or severe trauma within 4 weeks prior to the first dose of study drug;
- •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;
Arms & Interventions
Treatment Cohort
1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42 2. Lysosomal HSV virus injection (divided into a dose-escalation phase and a dose-expansion phase; in the dose-escalation phase, Group 1 took 106 pfu/mL and Group 2 took 108 pfu/mL, and in the dose-expansion phase the dose of lysosomal HSV virus with the highest MPR of the escalation phase was taken.) .. The dose of intralymph node injection of lysosomal HSV virus in patients was determined according to the size of metastatic lymph nodes, (diameter less than or equal to 1.5 cm, maximum 1 mL; diameter 1.5-2.5 cm, maximum 2 mL; diameter greater than 2.5 cm, maximum 4 mL). Two injections were given per patient, with each dose separated by 2 weeks. 3. Standard of care surgery
Intervention: Lysogenic HSV virus.
Treatment Cohort
1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42 2. Lysosomal HSV virus injection (divided into a dose-escalation phase and a dose-expansion phase; in the dose-escalation phase, Group 1 took 106 pfu/mL and Group 2 took 108 pfu/mL, and in the dose-expansion phase the dose of lysosomal HSV virus with the highest MPR of the escalation phase was taken.) .. The dose of intralymph node injection of lysosomal HSV virus in patients was determined according to the size of metastatic lymph nodes, (diameter less than or equal to 1.5 cm, maximum 1 mL; diameter 1.5-2.5 cm, maximum 2 mL; diameter greater than 2.5 cm, maximum 4 mL). Two injections were given per patient, with each dose separated by 2 weeks. 3. Standard of care surgery
Intervention: Tislelizumab
Treatment Cohort
1. Tislelizumab administration on days 1 and 22, and afatinib continuous administration from days 1 to 42 2. Lysosomal HSV virus injection (divided into a dose-escalation phase and a dose-expansion phase; in the dose-escalation phase, Group 1 took 106 pfu/mL and Group 2 took 108 pfu/mL, and in the dose-expansion phase the dose of lysosomal HSV virus with the highest MPR of the escalation phase was taken.) .. The dose of intralymph node injection of lysosomal HSV virus in patients was determined according to the size of metastatic lymph nodes, (diameter less than or equal to 1.5 cm, maximum 1 mL; diameter 1.5-2.5 cm, maximum 2 mL; diameter greater than 2.5 cm, maximum 4 mL). Two injections were given per patient, with each dose separated by 2 weeks. 3. Standard of care surgery
Intervention: Afatinib
Outcomes
Primary Outcomes
The incidence of dose-limiting toxicity (DLT) Incidence.
Time Frame: Intraoperative.
Dose-Limiting Toxicity (DLT) is the maximum safe dose of radiotherapy that a patient can tolerate in an experiment.
Secondary Outcomes
- Major Pathologic Response(Intraoperative.)
- Pathologic Complete Response(Intraoperative.)
- Objective Response Rate(Up to 8 weeks)
- Adverse events(Up to 12 weeks)
- Disease-free Survival(1 year)