| Eligibility |
Inclusion Criteria:
- Aged = 18 years old, male or female;
- Subjects with histopathologically confirmed recurrent/metastatic nonkeratinizing
differentiated or undifferentiated NPC;
- Subjects with diseases of clinical stage IVB [Staging System of American Joint
Committee on Cancer (AJCC) (8th edition)] who have received first line of
platinum-containing combination chemotherapy and second line of monotherapy or failure
of 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 that
have been treated with local therapies, such as radiotherapy, cannot be considered as
measurable lesions;
- Tissue or tissue samples must be provided for biomarker analysis. Newly obtained
tissues are preferred, and archived paraffin slices are acceptable for patients who do
not have newly obtained tissues;
- Adequate organ and bone marrow function, as defined below: a) Hematology: neutrophil
count (NEUT #) = 1.5 × 10^9/L; platelet count (PLT) = 90 × 10^9/L; hemoglobin
concentration = 9 g/dL; b) Hepatic function: aspartate aminotransferase (AST) and
alanine 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: international
normalized ratio (INR) = 1.5 and activated partial thromboplastin time (APTT) = 1.5 ×
ULN;
- Subjects who have taken chemotherapeutic drugs which should be discontinued for = 4
weeks before the first dose (mitomycin or nitrosoureas should be discontinued for = 6
weeks); received surgery, molecular targeted therapy, traditional Chinese medicine
therapy with anti-tumor indications, radiotherapy, and anti-tumor therapy with
immunostimulatory effect which should be discontinued for 4 weeks or more than 5
half-lives; and antibody drugs which should be discontinued for = 12 weeks (= 4 weeks
after discontinuation of bevacizumab or nimotuzumab is acceptable); moreover, all
treatment-emergent adverse events (TEAEs, except for alopecia) should have stabilized
and 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 medical
contraception during the study and for 6 months after the end of dosing. Women of
childbearing potential must have a negative pregnancy test within 72 h before the
first dose;
- Subjects voluntarily participate in the study, sign the ICF, and will be able to
comply with the protocol-specified visits and relevant procedures.
Exclusion Criteria:
- Subjects with locally advanced disease will not be screened if they can receive
radical 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 intramucosal
cancer, breast cancer, localized prostate cancer that have been cured and have not
recurred within 5 years, which are considered acceptable for enrollment by the
investigator);
- History of severe allergic diseases, history of serious drug allergy, and known
allergy to macromolecular protein preparations or any component of the KL-A167
Injection 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-cell
co-stimulation or checkpoint pathway);
- Palliative radiotherapy (except for bone metastases) scheduled for symptom control
during 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 transplantation
or autologous hematopoietic stem cell transplantation within 3 months prior to the
first 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 not
limited to, immune-related neurological disorders, multiple sclerosis, autoimmune
(demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus
erythematosus (SLE), connective tissue disorder, scleroderma, inflammatory bowel
diseases including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic
epidermal necrolysis (TEN), or Stevens-Johnson syndrome;
- Subjects with hyperthyroidism and organic thyroid disease will not be screened, but
those with hypothyroidism treated with a stable dose of thyroid hormone replacement
therapy can be enrolled;
- Systemic treatment with steroids (at a dose equivalent to prednisone > 10 mg/day) or
other immunosuppressants within 14 days prior to the first dose; Note: Adrenaline
replacement therapy at doses equivalent to prednisone = 10 mg/day is allowed for
subjects without active immune disease. Topical, intraocular, intra-articular,
intranasal, or inhaled corticosteroids (with minimal systemic absorption) are
permitted; and short-term use of corticosteroids for prophylaxis (e.g., contrast
allergy) or treatment of non-autoimmune conditions (e.g., delayed-type
hypersensitivity caused by contact allergens) is permitted.
- Subjects with serious medical conditions, such as cardiovascular disorders like Grade
III or higher abnormal cardiac function (NYHA criteria), ischemic heart disease (such
as myocardial infarction or angina pectoris), poorly controlled diabetes mellitus
(fasting serum glucose = 10 mmol/L), poorly controlled hypertension (systolic blood
pressure > 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 the
investigational 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 of
the assay);
- Known history of human immunodeficiency virus (HIV)-positive or known history of
acquired immunodeficiency syndrome (AIDS);
- Subjects with known history of interstitial pneumonia, noninfectious pneumonitis, or
highly suspicious of interstitial pneumonia; or subjects with conditions that may
interfere with the detection or management of suspected drug-related pulmonary
toxicity; and asymptomatic subjects with prior drug-induced or radiation noninfectious
pneumonitis are allowed to be enrolled;
- Active pulmonary tuberculosis, or previous history of tuberculosis infection but not
controlled by treatment;
- Subjects who have received immunotherapy and experienced = Grade 3 immune-related
adverse 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 used
during the study;
- Previous confirmed history of neurological or mental disorders, including epilepsy or
dementia;
- 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 the
opinion of the investigator.
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