KL-A167 Injection in Recurrent or Metastatic Nasopharyngeal Carcinoma

Inclusion Criteria:

• Aged ≥ 18 years old, male or female;
• Subjects with histopathologically confirmed recurrent/metastatic nonkeratinizingdifferentiated or undifferentiated NPC;
• Subjects with diseases of clinical stage IVB [Staging System of American JointCommittee on Cancer (AJCC) (8th edition)] who have received first line ofplatinum-containing combination chemotherapy and second line of monotherapy or failureof combination therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1;
• Expected survival ≥ 12 weeks;
• Subjects with at least one measurable lesion according to RECIST 1.1, and lesions thathave been treated with local therapies, such as radiotherapy, cannot be considered asmeasurable lesions;
• Tissue or tissue samples must be provided for biomarker analysis. Newly obtainedtissues are preferred, and archived paraffin slices are acceptable for patients who donot have newly obtained tissues;
• Adequate organ and bone marrow function, as defined below: a) Hematology: neutrophilcount (NEUT #) ≥ 1.5 × 10^9/L; platelet count (PLT) ≥ 90 × 10^9/L; hemoglobinconcentration ≥ 9 g/dL; b) Hepatic function: aspartate aminotransferase (AST) andalanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); total bilirubin (TBIL) ≤ 1.5 × ULN; ALT and AST ≤ 5 × ULN for subjects with liver metastases; TBIL ≤ 2 × ULN for subjects with liver metastases or Gilbert's syndrome; c) Renal function:creatinine clearance (CCR) ≥ 50 mL/min; d) Coagulation function: internationalnormalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 ×ULN;
• Subjects who have taken chemotherapeutic drugs which should be discontinued for ≥ 4weeks before the first dose (mitomycin or nitrosoureas should be discontinued for ≥ 6weeks); received surgery, molecular targeted therapy, traditional Chinese medicinetherapy with anti-tumor indications, radiotherapy, and anti-tumor therapy withimmunostimulatory effect which should be discontinued for 4 weeks or more than 5half-lives; and antibody drugs which should be discontinued for ≥ 12 weeks (≥ 4 weeksafter discontinuation of bevacizumab or nimotuzumab is acceptable); moreover, alltreatment-emergent adverse events (TEAEs, except for alopecia) should have stabilizedand recovered to the level specified in the eligibility criteria or ≤ Grade 1 toxicity (NCI CTCAE V.5.0);
• Subjects of childbearing potential (male or female) must use effective medicalcontraception during the study and for 6 months after the end of dosing. Women ofchildbearing potential must have a negative pregnancy test within 72 h before thefirst dose;
• Subjects voluntarily participate in the study, sign the ICF, and will be able tocomply with the protocol-specified visits and relevant procedures.

Exclusion Criteria:

• Subjects with locally advanced disease will not be screened if they can receiveradical treatment such as surgery, radical radiotherapy, or radical chemoradiotherapy;
• Metastases to central nervous system;
• History of other malignancies (except for non-melanoma skin cancer in situ,superficial bladder cancer, cervical cancer in situ, gastrointestinal intramucosalcancer, breast cancer, localized prostate cancer that have been cured and have notrecurred within 5 years, which are considered acceptable for enrollment by theinvestigator);
• History of severe allergic diseases, history of serious drug allergy, and knownallergy to macromolecular protein preparations or any component of the KL-A167Injection formulation;
• Prior treatment with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody,anti-CTLA-4 antibody, or CAR-T cells (or any other antibody acting on T-cellco-stimulation or checkpoint pathway);
• Palliative radiotherapy (except for bone metastases) scheduled for symptom controlduring the study;
• Other systemic anti-tumor therapies that may be received during the study;
• Prior anti-tumor vaccine within 3 months prior to the first dose;
• Allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantationor autologous hematopoietic stem cell transplantation within 3 months prior to thefirst dose;
• Active infection, or unexplained fever before the first dose;
• Systemic use of antibiotics within 1 week prior to signing the ICF;
• Any active autoimmune disease or history of autoimmune disease, including, but notlimited to, immune-related neurological disorders, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupuserythematosus (SLE), connective tissue disorder, scleroderma, inflammatory boweldiseases including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxicepidermal necrolysis (TEN), or Stevens-Johnson syndrome;
• Subjects with hyperthyroidism and organic thyroid disease will not be screened, butthose with hypothyroidism treated with a stable dose of thyroid hormone replacementtherapy can be enrolled;
• Systemic treatment with steroids (at a dose equivalent to prednisone > 10 mg/day) orother immunosuppressants within 14 days prior to the first dose; Note: Adrenalinereplacement therapy at doses equivalent to prednisone ≤ 10 mg/day is allowed forsubjects without active immune disease. Topical, intraocular, intra-articular,intranasal, or inhaled corticosteroids (with minimal systemic absorption) arepermitted; and short-term use of corticosteroids for prophylaxis (e.g., contrastallergy) or treatment of non-autoimmune conditions (e.g., delayed-typehypersensitivity caused by contact allergens) is permitted.
• Subjects with serious medical conditions, such as cardiovascular disorders like GradeIII or higher abnormal cardiac function (NYHA criteria), ischemic heart disease (suchas myocardial infarction or angina pectoris), poorly controlled diabetes mellitus (fasting serum glucose ≥ 10 mmol/L), poorly controlled hypertension (systolic bloodpressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg), and ejection fraction < 50% by echocardiography;
• QTc interval > 450 msec for males and > 470 msec for females;
• Abnormal ECG findings and additional risks associated with the use of theinvestigational product in the opinion of the investigator;
• Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL) or hepatitis C (positive for hepatitis C antibody and HCV RNA above the lower limit of detection ofthe assay);
• Known history of human immunodeficiency virus (HIV)-positive or known history ofacquired immunodeficiency syndrome (AIDS);
• Subjects with known history of interstitial pneumonia, noninfectious pneumonitis, orhighly suspicious of interstitial pneumonia; or subjects with conditions that mayinterfere with the detection or management of suspected drug-related pulmonarytoxicity; and asymptomatic subjects with prior drug-induced or radiation noninfectiouspneumonitis are allowed to be enrolled;
• Active pulmonary tuberculosis, or previous history of tuberculosis infection but notcontrolled by treatment;
• Subjects who have received immunotherapy and experienced ≥ Grade 3 immune-relatedadverse reactions (ADRs);
• Use of any active vaccine against infectious diseases (e.g. influenza vaccine,varicella vaccine, etc.) within 4 weeks prior to the first dose or planned to be usedduring the study;
• Previous confirmed history of neurological or mental disorders, including epilepsy ordementia;
• History of definite drug abuse or alcohol abuse within 3 months;
• Pregnant or lactating women;
• Participation in other clinical trials within 1 month prior to the first dose;
• Other factors that may affect the efficacy or safety evaluation of this study in theopinion of the investigator.