TQB2618 Injection Combined With Penpulimab Injection in the Treatment of Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma

Inclusion Criteria:

• Histologically or cytologically confirmed nasopharyngeal carcinoma, stage IVb asdefined by the AJCC TNM staging system for nasopharyngeal carcinoma, 8th edition in 2017 or subjects with recurrent nasopharyngeal carcinoma who were not suitable forlocal therapy (For neoadjuvant/adjuvant therapy and radical concurrentchemoradiotherapy, if the disease progresses during treatment or within 6 months afterthe treatment completion, it should be counted as a failure of first-line treatment ofthe original plan, and if it exceeds 6 months, it cannot be counted as first-linetreatment failure. Alterations of treatment regimen due to drug intolerance are notdefined as treatment failure).
• The first part of enrolled patients shall also meet the following requirements:

1. At least received first-line treatment for recurrent/metastatic lesions, and thelast anti-tumor treatment before enrollment had evidence of imaging progress inline with RECIST 1.1 standard;
2. At least have received platinum containing chemotherapy and immunocheckpointinhibitors (anti-PD-1 monoclonal antibody/anti-PD-L1 monoclonal antibody, etc.)in the past and failed treatment, and there is evidence of imaging progress thatmeets the RECIST 1.1 standard. Platinum containing chemotherapy and immunotherapycan be used during palliative treatment for recurrent/metastatic lesions, orduring radical treatment for locally advanced diseases.
3. Immunotherapy for recurrent/metastatic lesions shall not exceed 2 lines (Forneoadjuvant/adjuvant therapy and radical concurrent chemoradiotherapy, if thedisease progresses during treatment or within 6 months after the treatmentcompletion, it should be counted as a failure of first-line treatment of theoriginal plan, and if it exceeds 6 months, it cannot be counted as first-linetreatment. Failure. Alterations of treatment regimen due to drug intolerance donot defined as treatment failure
4. For the latest immunotherapy before enrollment, if it is aimed atrecurrence/metastasis, the best efficacy is at least SD (≥ 6 weeks) or confirmedPR or immunotherapy duration ≥ 12 weeks.

• The second part of the enrolled patients also need to meet the following requirements:

1. Have not received systemic antitumor therapy for recurrent/metastaticnasopharyngeal carcinoma before;
2. No previous treatment with immune checkpoint inhibitors (anti PD-1 monoclonalantibody/anti PD-L1 monoclonal antibody, etc.). Those who have used no more thanone immune checkpoint inhibitor (limited to CTLA-4/PD-1/PD-L1 monoclonalantibody, not including bispecific antibody, not including Penpulimab injection)in the stage of locally advanced radical treatment can be included if they meetthe following criteria:
3. If used in the induction phase (with or without other drugs), the besteffect in the induction phase is at least PR;
4. If used during radical radiochemotherapy/radiotherapy or subsequentmaintenance stage, there is no progress during treatment and within one yearafter stopping treatment

• At least one measurable lesion confirmed according to RECIST 1.1 criteria;
• The function of main organs are well and meet the following standards:

1. Routine Blood routine examination standards (without blood transfusion orcorrection with hematopoietic stimulating factor drugs within 14 days before theexamination):
2. Hemoglobin (HGB) ≥90 g/L;
3. Absolute value of neutrophil (NEUT) ≥1.5×109/L;
4. Platelets count (PLT) ≥ 100×109/L.
5. The biochemical examination shall meet the following standards:
6. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN) (Patientswith Gilbert syndrome ≤ 3 × ULN);
7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ×ULN. If it is accompanied by liver metastasis, ALT and AST ≤ 5 × ULN;
8. Serum creatinine (CR) ≤ 1.5 × ULN or Creatinine clearance (CCR) ≥ 60 ml/min;
9. Blood coagulation function or thyroid function test should meet the followingstandards: Prothrombin time (PT), activated partial thromboplastin time (APTT),international normalized ratio (INR)≤1.5×ULN (no anticoagulant therapy);
10. Thyroid Stimulating Hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should beexamined. If T3 and T4 levels are normal, it can be selected.
11. Heart color Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%.

• Female subjects of reproductive age should agree that they must conduct contraceptivemeasures (such as intrauterine devices, contraceptives, or condoms) during and for 6months after the study; Female subjects should have a negative serum/urine pregnancytest within 7 days prior to study enrollment and must be non-lactating; Male subjectsshould agree that they must conduct contraception during the study period and for 6months after the study.

Exclusion Criteria:

• Combined diseases and medical history:

1. Other malignant tumors have occurred or are currently suffering from othermalignant tumors within 5 years before the first medication, except for fullytreated non-melanoma skin cancer, cervical carcinoma in situ and papillarythyroid carcinoma;
2. Unresolved toxicities greater than CTC AE grade 1 due to any prior therapy,excluding alopecia, neurotoxic sequelae associated with prior platinum therapy;
3. Received major surgical treatment, obvious traumatic injury (excluding needlebiopsy, endoscopic biopsy, etc.) within 28 days before the first drug;
4. Arterial/venous thrombotic events, such as cerebrovascular accident (includingtransient ischemic attack, cerebral hemorrhage, cerebral infarction), deep veinthrombosis and pulmonary embolism, occurred within 6 months before the firstdrug;
5. Active pulmonary tuberculosis, history of idiopathic pulmonary fibrosis,organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiringtreatment, or active pneumonia with clinical symptoms;

• Cancer-related symptoms and treatment:

1. Received NMPA-approved Chinese patent medicines with anti-tumor indications inthe drug insert within 2 weeks prior to the first administration;
2. Received surgery, chemotherapy, radiotherapy or other anti-cancer therapy within 3 weeks before the start of study treatment (the washout period is calculatedfrom the end of the last treatment); those who have received local radiotherapyin the past can be enrolled if they meet the following conditions: radiotherapyThe end of the study treatment is more than 3 weeks (more than 2 weeks for brainradiotherapy); and the target lesions selected in this study are not in theradiotherapy area; Or the target lesion is located in the radiotherapy area, butthe progress has been confirmed.
3. Previous treatment with anti-TIM-3 antibodies;
4. The nasopharyngeal lesions recurred after radiotherapy and receivedRe-radiotherapy;
5. maging (CT or MRI) shows that the tumor has invaded around important bloodvessels, and it is judged by the investigator that the tumor is very likely toinvade important blood vessels and cause fatal hemorrhage during the follow-upstudy;
6. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeateddrainage;
7. Known uncontrolled or symptomatic active central nervous system (CNS) metastasespresenting with clinical symptoms, cerebral edema, spinal cord compression,cancerous meningitis, leptomeningeal disease, and/or progressive growth. Patientswith a history of CNS metastases or spinal cord compression were eligible if theywere clearly treated and clinically stable after 4 weeks of discontinuation ofanticonvulsants, steroids, or dehydrating agents prior to the first dose of thestudy.