Iparomlimab and Tuvonralimab Injection for Untreated Locally Advanced Nasopharyngeal Carcinoma

Exclusion Criteria

• •Received anti-tumor cytotoxic drug therapy, biological drug therapy (such as monoclonal antibodies), immunotherapy (such as interleukin-2 or interferon), or other investigational drug therapy within 4 weeks before enrollment, except for corticosteroids
• •Previously received anti-VEGFR and other vascular-targeted drug therapy
• •Judged by the researcher to have impaired immunity
• •Underwent major surgical operation within 4 weeks before enrollment or has not fully recovered from previous surgery (the definition of major surgical operation refers to grade 3 and 4 operations specified in the "Administrative Measures for Clinical Application of Medical Technologies" implemented on May 1, 2009)
• •Toxic reactions from previous anti-tumor treatment have not recovered to CTCAE grade 0-1, except for the following situations:
• •1. Alopecia;
• •2. Pigmentation;
• •3. Peripheral neurotoxicity has recovered to \< CTCAE grade 2;
• •4. Long-term toxicity caused by radiotherapy, which cannot recover as judged by the researcher
• •Grade 3-4 bleeding or high bleeding risk caused by underlying malignant tumors (such as but not limited to tumors surrounding or infiltrating large blood vessels, i.e., carotid artery, jugular vein) and/or specific other high-risk characteristics (e.g., arteriovenous fistula)
• •Previously or currently suffering from other malignant tumors (except for well-controlled non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ, and other malignant tumors that have been effectively controlled without treatment in the past five years)
• •Subjects with any active autoimmune disease or a history of autoimmune diseases (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or asthma that has been completely relieved in childhood and do not require any intervention in adulthood can be included; those with asthma requiring medical intervention with bronchodilators cannot be included)
• •Previously used anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, or anti-CTLA-4 antibody (or any other antibody acting on T cell co-stimulation or checkpoint pathways)
• •Subjects with active pulmonary tuberculosis (TB) who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening
• •Received any anti-infective vaccine (such as influenza vaccine, varicella vaccine, etc.) within 4 weeks before enrollment
• •Pregnant or lactating women
• •HIV positive
• •Patients with acute or chronic active hepatitis B or C infection, with hepatitis B virus (HBV) DNA \> 2000 IU/ml or 10⁴ copies/ml, hepatitis C virus (HCV) RNA \> 10³ copies/ml; simultaneous positivity for hepatitis B surface antigen (HbsAg) and anti-HCV antibody. Those who are below the above standards after nucleotide antiviral treatment can be enrolled
• •Any life-threatening bleeding event within the previous 3 months, including those requiring blood transfusion, surgery or local treatment, and continuous drug treatment
• •A history of arterial or venous thromboembolic events within the previous 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other serious thromboembolic history. Except for those with implantable venous access port or catheter-derived thrombosis, or superficial venous thrombosis, whose thrombosis is stable after conventional anticoagulant therapy. Prophylactic use of low-dose low molecular weight heparin (such as enoxaparin 40mg/day) is allowed
• •Uncontrolled hypertension, with systolic blood pressure \> 140mmHg or diastolic blood pressure \> 90mmHg after optimal medical treatment, or a history of hypertensive crisis or hypertensive encephalopathy
• •Used aspirin (\> 325mg/day) or other drugs known to inhibit platelet function such as dipyridamole or clopidogrel for 10 consecutive days within 2 weeks before the first dose
• •Symptomatic congestive heart failure (New York Heart Association class II-IV). Symptomatic or poorly controlled arrhythmias. A history of congenital long QT syndrome or corrected QTc \> 500ms at screening (calculated using the Fridericia method)
• •Severe bleeding tendency or coagulation dysfunction, or receiving thrombolytic therapy
• •A history of gastrointestinal perforation and/or fistula within the previous 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive intestinal resection (partial colon resection or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea
• •Known allergy to any component of PD-1 and CTLA-4 antibodies; or have had a severe allergic reaction to other monoclonal antibodies in the past
• •Any other clinically significant diseases or conditions that the researcher believes may affect protocol compliance, or affect the subject's signing of the informed consent form (ICF), or make them unsuitable for participating in this clinical trial