Envafolimab Combined With Chemoradiotherapy and Recombinant Human Endostatin for LA-NPC.

This is a single-center, prospective, single-arm phase II clinical study. Patients with high-risk locally advanced stage III-IVA (8th AJCC/UICC staging) primary nasopharyngeal carcinoma, i.e., T4N+ or N2-3, or pretreatment EBV-DNA ≥4000 copies/ml, or lymph node extra-envelope invasion grade 3 (invasion of muscle skin, etc.) are enrolled. After being screened to meet the enrolment criteria and signing the informed consent form, they will receive 3 cycles of induction therapy with envafolimab combined with recombinant human vascular endothelial inhibitor and gemcitabine and cisplatin, followed by cisplatin-concomitant radiotherapy, and 8 cycles of adjuvant therapy with envafolimab after radiotherapy.

Inclusion criteria

• ECOG score 0-1.
• Aged 18-65 years, male or non-pregnant female;
• Pathologically confirmed diagnosis of nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, WHO type II or III) without the need to detect MSI and dMMR status.
• high-risk locally advanced stage III-IVA (8th AJCC/UICC staging), i.e., T4N+ or N2-3, or pretreatment EBV-DNA ≥4000 copies/ml, or lymph node extra-envelope invasion grade 3 (invasion of muscle skin, etc.), treatment-naive nasopharyngeal carcinoma patients.
• MRI data of nasopharynx and neck before enrollment, and measurable lesions;
• Agree to provide a previously stored tumor tissue specimen or biopsy to collect tumor lesion tissue and send it to the central laboratory for PD-L1 IHC testing.
• Agree to undergo EBV antibody and EBV-DNA quantitative testing before receiving treatment.
• Hematology: WBC ≥ 4000/μL, neutrophils ≥ 2.000/μL, hemoglobin ≥ 9 g/dL, platelets ≥ 100,000/μL;
• Liver function: ALT, AST < 1.5 times the upper limit of normal (ULN), total bilirubin < 1.5 × ULN;
• Renal function: serum creatinine < 1.5 × ULN.
• Patients have signed the informed consent form and are willing and able to comply with the study plan visits, treatment plan, laboratory tests and other study procedures;

Exclusion criteria

• Patients with recurrent nasopharyngeal carcinoma and distant metastasis.
• Pathology was keratinizing squamous cell carcinoma (WHO classification type I).
• Patients who have undergone radiotherapy or systemic chemotherapy;
• Pregnant or lactating women, in the reproductive period without effective contraceptive measures;
• HIV positive.
• Having had other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ);
• Patients who have been treated with inhibitors of immune regulatory points (CTLA-4, PD-1, PD-L1, etc.);
• Patients need long-term use of immunosuppressive drug therapy, or systemic or local use of immunosuppressive doses of corticosteroids complications;
• Patients with immunodeficiency disease, history of organ transplantation (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or complete remission of asthma in childhood, without any intervention after adulthood can be included; patients with asthma requiring bronchodilators for medical intervention can not be included;
• Use of excessive doses of glucocorticoids within 4 weeks.
• Laboratory test values within 7 days before enrollment do not meet the relevant criteria;
• Patients with significantly low heart, liver, lung, kidney and bone marrow function.
• Any other diseases or conditions are contraindications to recombinant human vascular endothelial inhibitors, chemoradiotherapy, immunotherapy (such as active phase of infection, within 6 months after myocardial infarction, symptomatic heart disease including unstable angina pectoris, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy);
• Any arterial thrombosis, embolism or ischemia within 6 months before inclusion for treatment, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack;
• Severe, uncontrolled medical illness and infection.
• Concurrent use of other investigational drugs or ongoing other clinical trials;
• Refusing or unable to sign the informed consent form to participate in the trial.
• Personality or mental disorders, no civil capacity or limited civil capacity;
• Hepatitis B surface antigen (HBsAg) positive and peripheral blood hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 1000cps/ml.
• Patients who tested positive for HCV antibody were included in the study only if they tested negative for HCV RNA by polymerase chain reaction.