| Eligibility |
Inclusion Criteria:
- The ages at the time of signing the informed consent are = 18 years old and = 75 years
old, regardless of gender.
- Patients with nasopharyngeal carcinoma diagnosed definitively by histology or
cytology.
- Recurrent or metastatic nasopharyngeal carcinoma:Nasopharyngeal carcinoma patients
with distant metastasis at the time of initial diagnosis (stage IVB nasopharyngeal
carcinoma as defined by the 8th Edition of the staging system of Union for
International Cancer Control and American Cancer Joint Committee); or nasopharyngeal
carcinoma patients with local recurrence and/or distant metastasis more than 6 months
after the end of previous radical treatment.Have not received systematic treatment for
recurrent or metastatic nasopharyngeal carcinoma before; those who have local
recurrence are not suitable for local treatment or have been treated locally.
- Eastern Cooperative Oncology Group (ECOG) performance status is 0 ~ 1 score, and the
expected survival time is = 12 weeks.
- At least one measurable lesion according to RECIST 1.1; the lesions that have received
radiotherapy are not selected as target lesions.
- Patients must provide tissues or tissue specimens for biomarker analysis during the
screening period, and the freshly obtained tissues are preferred. Patients who cannot
obtain the fresh tissues can provide archived paraffin sections.
- Significant organ functions meet the following requirements:a)Blood routine:
Neutrophil count (NEUT) = 1.5×109/L; platelet count (PLT)=100×109/L; hemoglobin = 90
g/L.b)Liver function: Aspartate aminotransferase (AST), alanine aminotransferase (ALT)
= 2.5 × upper limit of normal value (ULN); total bilirubin (TBIL) = 1.5×ULN; for
patients with liver metastasis, ALT and AST = 5×ULN; for patients with liver
metastasis or Gilbert syndrome, TBIL = 3×ULN.c)Albumin = 30 g/L.d)Renal function:
creatinine clearance rate (CrCl) = 60 ml/min (using standard Cockcroft-Gault
formula).e)Coagulation function: International standardized ratio (INR) = 1.5×ULN;
activated partial thromboplastin time (APTT) = 1.5×ULN.
- Those who have child-bearing potential during the study period and within 6 months
after the end of the last dose study (both men and women) must take effective medical
contraceptive measures.
- Patients voluntarily participate in this study, sign informed consent, and are able to
comply with the visits and related procedures specified in the protocol.
Exclusion Criteria:
- Patients with pathologically diagnosed nasopharyngeal adenocarcinoma or sarcoma.
- Central nervous system metastasis is present at the time of screening.
- Uncontrollable tumor-related pain.
- Other malignant tumors before randomization (except those who have non-melanoma in
situ skin cancer, superficial bladder cancer, cervical cancer in situ, breast cancer,
localized prostate cancer, etc., which have been cured and not recurred within 3
years, and the investigator considers those who can be enrolled).
- It is known that there is a history of allergy to any ingredient of KL-A167 injection
or severe hypersensitivity to other monoclonal antibodies, or hypersensitivity to
gemcitabine, cisplatin and any excipients.
- Have received any of the following treatment:a)Previous immunotherapy, including
immune checkpoint inhibitors (such as PD-1 antibody, PD-L1 antibody, CTLA-4 antibody,
etc.), immune checkpoint agonists, immune cell therapy and other treatments targeting
at the immune mechanism of tumor.b)Any clinical study drugs within 4 weeks before
randomization.c)Participation in another clinical study concurrently, unless it is an
observational (non-interventional) clinical study or an interventional clinical study
follow-up.d)The last dose of non-systemic anticancer therapy (including local
radiotherapy, radiofrequency ablation, anti-tumor Chinese patent medicine, etc.)
within 2 weeks before randomization.e)Those who were vaccinated with anti-tumor
vaccine previously or have been vaccinated with any active vaccine (such as influenza
vaccine, varicella vaccine, etc.) within 4 weeks before randomization or plan to do so
during the study period.f)Major surgery (except diagnosis of nasopharyngeal carcinoma)
or severe trauma was performed within 4 weeks before randomization.g)Any blood
components, anemia correcting drugs (including but not limited to drugs which
supplement hematopoietic raw materials, raise red blood cells and raise hemoglobin),
drugs which raise white blood cells and platelets were used within 2 weeks before
randomization.
- Concomitant diseases that may affect protocol compliance or trial results,
including:a)Major cardiovascular diseases, such as Grade II and above cardiac
dysfunction (NYHA standard); myocardial infarction, unstable arrhythmia or unstable
angina pectoris within 3 months before randomization; previous history of myocarditis
or cardiomyopathy; echocardiography showed ejection fraction < 50%; QTc interval, male
> 450 msec, female > 470 msec; ECG examination is abnormal and the investigator
considers there is additional risk.b) Symptomatic hypercalcemia (serum calcium> 2.9
mmol/L ).
- The toxicity of previous anti-tumor treatment has not recovered to = CTCAE version 5.0
Level 1 or the level specified in the inclusion/exclusion criteria (except for hair
loss, fatigue, sequelae of neurotoxicity related to previous platinum treatment,
specific laboratory investigation abnormalities and other conditions that the
investigator judges there is no safety risk).
- The history of allogeneic organ transplantation or hematopoietic stem cell
transplantation is known.
- Severe chronic or active infections (including active tuberculosis, etc.) occurred
within 2 weeks before randomization, which required systemic antibiotics or antiviral
treatment.
- Any patient with active autoimmune disease or a history of autoimmune disease and
possible recurrence, including but not limited to neurological diseases related to
immunity, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre
syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue
diseases, scleroderma, inflammatory bowel diseases including Crohn's disease and
ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis (TEN) or
Stevens-Johnson syndrome.Note: Patients with the following diseases are not excluded,
and can be screened following other inclusion and exclusion criteria:a)Type 1 diabetes
that can be controlled by stable dose of insulin.b)Hypothyroidism that can be
controlled by hormone replacement therapy alone.c)Skin diseases that do not require
systemic treatment (e.g. vitiligo, psoriasis, hair loss).d)Any other disease that is
not expected to recur in the absence of external triggers.
- Treated with systemic immuno-agonists (including but not limited to interferon or
IL-2) or received systemic treatment with steroid hormones (equivalent to prednisone >
10 mg/day) or other immunosuppressants within 2 weeks before randomization.Note:
Subjects without active immune diseases are allowed to receive steroid hormone
replacement therapy with a dose equivalent to prednisone = 10 mg/day. Topical,
intraocular, intra-articular, intranasal or inhaled corticosteroids (extremely low
systemic absorption) are allowed; short-term use of corticosteroids is allowed to
prevent (such as allergy to contrast media) or treat non-autoimmune conditions (such
as delayed type hypersensitivity caused by exposure to allergens).
- Patients have active hepatitis B (HBsAg positive, but if HBV DNA detected by each
study site = 1×103 copy number/ml or lower than the lower limit of reference value,
patients are allowed to be enrolled) or hepatitis C (hepatitis C antibody positive,
but if HCV RNA lower than the lower limit of detection method, patients are allowed to
be enrolled).
- The history of positive test for human immunodeficiency virus (HIV) or acquired
immunodeficiency syndrome (AIDS) is known.
- For patients with known history of interstitial lung disease (such as idiopathic
pulmonary fibrosis, sarcoidosis, etc.) and non-infectious pneumonia (such as
intensified pneumonia, idiopathic pneumonia, etc.), those who had drug-induced or
radiation-induced rather than infectious pneumonia but were asymptomatic are allowed
to be enrolled in the group.
- Grade 2 or above peripheral nerve disease , defined according to CTCAE 5.0 standard.
- Pregnant or lactating women.
- Other clinically significant underlying diseases that may affect drug administration
and protocol compliance (such as poorly controlled diabetes/hypertension, pleural
effusion/pericardial effusion/ascites requiring repeated drainage, drug or alcohol
abuse, etc.) considered by the investigator, as well as other factors that may affect
the efficacy or safety assessment of this study.
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