Cadonilimab (AK104) in the Treatment of Nasopharyngeal Carcinoma

Inclusion Criteria:

1. The age at the time of enrollment is more than 18 years old and less than 75 yearsold, both male and female.
2. The Eastern Cancer Cooperation Organization (ECOG) physical fitness score was 0 or 1.
3. The expected survival period is more than 3 months.
4. Nasopharyngeal carcinoma confirmed by histology or cytology.
5. The subject has previously received treatment with PD-1 inhibitor and failed withoutindication of radical local treatment. According to the evaluation standard of curative effect of solid tumor, RECIST v l L Atleast one measurable lesion.

Exclusion Criteria:

1. Except for nasopharyngeal carcinoma, the subjects had other malignant tumors within 2years before enrollment. Subjects with other tumors that have been cured by localtreatment, such as basal or cutaneous squamous cell carcinoma, superficial bladdercancer, cervical or breast cancer in situ, are not excluded.
2. He participated in the treatment of experimental drugs within 4 weeks before the firststudy administration.
3. Patients with active autoimmune diseases that require systematic treatment in the pasttwo years (such as the use of disease improvement drugs, corticosteroids,immunosuppressive therapy), and replacement therapy (such as thyroxine, insulin, orphysiological corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) are not considered as a systemic treatment.
4. Have a history of immune deficiency; HIV antibody test positive; At present, systemiccorticosteroids or other immunosuppressants are being used for a long time.
5. Active tuberculosis (TB) is known. Subjects suspected of active TB should be excludedfrom active TB.
6. The history of allogeneic organ transplantation and allogeneic hematopoietic stem celltransplantation are known.
7. The untreated active hepatitis B subjects (HBsAg positive and HBV-DNA more than 1000copies/ml (200 IU/ml) or higher than the lower detection limit, whichever is higher)are required to receive anti hepatitis B virus treatment during the study treatmentperiod; Active hepatitis C subjects (HCV antibody positive and HCV-RNA level higherthan the lower limit of detection).
8. Major surgical operation or serious injury occurred within 30 days before the firstadministration, or major surgical operation planner (determined by the researcher)within 30 days after the first administration; Minor local operations (excludingcentral venous catheterization via peripheral vein puncture) were performed within 3days before the first administration.
9. There is central nervous system metastasis.
10. There are currently uncontrolled concomitant diseases, including but not limited tosymptomatic congestive heart failure (grade 2 and above determined according to thefunctional classification of the New York Heart Association), unstable anginapectoris, acute myocardial ischemia, poorly controlled arrhythmia, decompensated livercirrhosis, nephrotic syndrome, uncontrolled metabolic disorder, severe active pepticulcer disease or gastritis, Mental illness/social condition that may limit thesubject's compliance with the research requirements or affect the subject's ability toprovide written informed consent.
11. There was a history of myocarditis, cardiomyopathy and malignant arrhythmia in thepast. Unstable angina pectoris, congestive heart failure or vascular disease (such asaortic aneurysm or peripheral venous thrombosis requiring surgical repair) that needshospitalization within 12 months before the first administration of the drug, or othercardiac damage that may affect the safety evaluation of the study drug (such as poorlycontrolled arrhythmia, myocardial infarction or ischemia); There is a history ofesophageal and gastric varices, serious ulcer, wound healing, gastrointestinalperforation, abdominal pain, gastrointestinal obstruction, abdominal abscess or acutegastrointestinal bleeding within 6 months before the first administration; Anyarterial thromboembolic event occurred within 6 months before the firstadministration, including venous thromboembolic generation of NC I CTCAE 5.0 grade 3and above, transient ischemic attack, cerebrovascular accident, hypertensive crisis orhypertensive encephalopathy; Acute exacerbation of chronic obstructive pulmonarydisease occurred within 1 month before the first administration; There is currentlyhypertension and after treatment with oral antihypertensive drugs, the systolic bloodpressure is more than 160 mmHg or the diastolic blood pressure is less than 100 mmHg.
12. Have a history of severe bleeding tendency or coagulation dysfunction; One monthbefore the first administration, there were blood symptoms with significant clinicalsignificance, including but not limited to gastrointestinal bleeding, hemoptysis,screening imaging showed that the tumor wrapped around important blood vessels or hadobvious necrosis and cavity, and the researcher believed that participating in thestudy might cause bleeding risk;
13. The toxicity of previous anti-tumor treatment has not been relieved, which is definedas that the toxicity has not returned to the level 0 or 1 of NC l CTCAE 5.0, or thelevel specified in the inclusion/exclusion criteria, except for the sequelae of hairloss and previous lead treatment related neurotoxicity. Subjects (such as hearingloss) who have irreversible toxicity and are not expected to worsen afteradministration of the study drug may be included in the study after consultation withthe medical examiner. Subjects with long-term toxicity caused by radiotherapy thatcannot be recovered according to the judgment of the researcher may be included in thestudy after consultation with the medical supervisor.
14. The live vaccine was vaccinated within 30 days before the first administration, or wasplanned to be vaccinated during the study period.
15. Known allergy to any component of any study drug; A history of severe hypersensitivityto other monoclonal antibodies is known.
16. Known history of mental illness, drug abuse, alcohol or drug abuse.
17. Pregnant or lactating women.
18. Any previous or current disease, treatment, or laboratory test abnormality may confusethe results of the study, affect the full participation of the subject in the study,or participation in the study may not be in the best interests of the subject.
19. Local or systemic diseases caused by non-malignant tumors, or diseases or symptomssecondary to tumors, which can lead to higher medical risk and/or uncertainty ofsurvival evaluation, such as tumor-like leukemia reaction (white blood cell count>20 X 109/L or cachexia performance (such as known weight loss of more than 10% in the 3months before screening), etc