A Clinical Study on Neoadjuvant Treatment of Resectable Head and Neck Squamous Carcinoma With Immune-targeted Therapy and Lysogenic HSV Virus

NCT06741982 | Recruiting Phase 1

• 1 other identifier: 2024-2497
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

HNSCC; Lysogenic HSV Virus; Neoadjuvant Therapy; Immunotherapy; Targeted Therapy

Outcome Measures

Primary Outcomes (1)

• The incidence of dose-limiting toxicity (DLT) Incidence.

  Dose-Limiting Toxicity (DLT) is the maximum safe dose of radiotherapy that a patient can tolerate in an experiment.

  Intraoperative.

Secondary Outcomes (5)

• 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

Study Arms (1)

Treatment Cohort

EXPERIMENTAL

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

Biological: Lysogenic HSV virus.; Drug: Tislelizumab; Drug: Afatinib

Interventions

Lysogenic HSV virus. BIOLOGICAL

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.

Also known as: Biological agent

Treatment Cohort

Tislelizumab DRUG

200mg IV Q3W

Also known as: Immunotherapy

Treatment Cohort

Afatinib DRUG

30mg PO QD

Also known as: Targeted therapy

Treatment Cohort

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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;
• 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 \<50%; QTc interval, \>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;
• 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;
• 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);
• Presence of an active infection, or fever of unknown origin during screening, 48 h prior to the first dose, or use of systemic antibiotics within 1 week prior to signing informed consent;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/ml or 104 copies/ml) or hepatitis C (hepatitis C antibody positive with HCV RNA above the lower limit of detection of the analytical method), or known history of positive human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS);

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (12)

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MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Biological Factors; tislelizumab; Immunotherapy; Afatinib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Xingchen Peng

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingchen Peng

CONTACT

18980606753; pxx2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Professor

Study Record Dates

• First Submitted: December 15, 2024
• First Posted: December 19, 2024
• Study Start: December 15, 2024
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: December 19, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)