| Eligibility |
Inclusion Criteria:
1. Male or female aged =18 years;
2. Understand and voluntarily sign the written informed consent form;
3. Study population:
Patients with histologically or cytologically confirmed locally advanced (stage
IIIB/IIIC) or metastatic (stage IV) NSCLC who cannot receive surgery or radical
concurrent chemoradiotherapy, based on the "8th Edition of the TNM Classification for
Lung Cancer" issued by the International Association for the Study of Lung Cancer
(IASLC); Have not received any prior systemic anti-tumor therapy for
advanced/metastatic disease; Subjects who received adjuvant or neoadjuvant therapy are
eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to
the development of stage IIIB, IIIC, IV.
Without mutation of epidermal growth factor receptor (EGFR), anaplastic lymphoma
kinase (ALK) or ROS-1; Note: The results of blood tests alone were not accepted;
4. With a life expectancy of more than 3 months;
5. With at least one measurable lesion (extra nodal lesions: long diameter > 10 mm, nodal
lesions: long diameter > 15 mm) confirmed by contrast-enhanced CT or MRI according to
RECIST v1.1;
6. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1;
7. Vital organ functions meet the following requirements (Reception of granulocyte
colony-stimulating factor (G-CSF) or pegylated granulocyte colony-stimulating factor
(PEG-G-CSF) or blood transfusion within 14 days prior to laboratory tests is not
permitted for prophylactic use):
Blood routine examination: absolute neutrophil count (ANC) = 1.5×109/L, hemoglobin
(HGB) = 90g/L, platelet count (PLT) = 100×109/L; Hepatic function: total bilirubin
(TBIL) = 1.5×ULN, and alanine transaminase (ALT) and aspartate amino transferase (AST)
= 2.5×ULN for all patients, or AST and ALT levels = 5×ULN for patients with liver
metastases; Renal function: serum creatinine (Cr) = 1.5×ULN or clearance of creatinine
(CCr) = 60 mL/min (Cr > 1.5×ULN); Coagulation function: international normalized ratio
(INR) = 1.5×ULN and Activated partial thromboplastin time (APTT) = 1.5×ULN; Thyroid
stimulating hormone (TSH) is within the normal range; If TSH is abnormal, free
triiodothyronine (FT3) and free thyroxine (FT4) should be normal or abnormal without
clinical significance;
8. Have provided tumor tissue specimens at or after the diagnosis of advanced or
metastatic disease (Formalin-fixed, paraffin-embedded (FFPE) tumor tissues that were
archived or freshly obtained within 6 months before the first dose; Tissue specimens
require PD-L1 expression to be evaluable).
Exclusion Criteria:
1. Cohort 1: Have a histologically confirmed diagnosis of NSCLC with predominant squamous
cells; Patients with mixed histology are not allowed if there is small cell component
in the specimen; Cohort2: Have a histologically confirmed diagnosis of NSCLC with
predominant Non-squamous cells; Mixed tumors will be categorized by the predominant
cell type; if small cell carcinoma, neuroendocrine carcinomas and sarcomas elements
are present, the subject is ineligible; Patients with mixed histology are allowed if
there is squamous component >50% in the specimen.
2. Has active central nervous system (CNS) metastases and/or carcinomatous meningitis in
the past or during screening, except for the following cases:
Subjects with asymptomatic brain metastases (i.e., no neurological symptoms, no
requirements for corticosteroids, and no lesion >1.5 cm) may participate but will
require regular imaging of the brain as a site of disease; Subjects with adequate
treatmen may participate provided they are clinically stable for at least 4 weeks, and
his nervous system and other clinical symptoms can return to the baseline level at
least 2 weeks before the first dose (Except for residual signs or symptoms related to
CNS therapy).
3. Subjects with spinal cord compression not curatively cured by surgery and/or
radiotherapy.
4. Had prior treatment with anti-PD-1, or PD-L1, or PD-L2, or CD137, or CTLA-4 antibody
or fusion protein or any other antibodies or drugs that specifically target T cell
co-stimulatory or checkpoint pathways.
5. Have suffered from interstitial lung disease, non-infectious pneumonia or uncontrolled
lung disease in the past 3 years, including but not limited to pulmonary fibrosis,
acute lung disease, etc. (Except chemotherapy-induced interstitial lung disease that
is currently asymptomatic).
6. Patients with uncontrolled or severe cardiovascular diseases, such as Class II-IV
congestive heart failure, unstable angina, myocardial infarction and other
cardiovascular diseases assessed by New York Heart Association (NYHA), uncontrolled
hypertension (systolic blood pressure = 180mmHg and/or diastolic pressure = 100mmHg),
poorly controlled arrhythmia (Including QTc interval male = 450 ms, female = 470 ms)
within 6 months before the first dose.
7. Subjects with symptomatic ascites, pericardial effusion or pleural effusion whose
clinical status is stable for more than 1 month after receiving treatment (including
therapeutic chest X-ray or puncture) can be enrolled.
8. Subjects who are using or have recently used (within 7 days before the first dose of
study drug) aspirin therapy, or is unable to interrupt nonsteroidal anti-inflammatory
drugs (NSAIDs) during the study. (apply to cohort 1)
9. Is unable or unwilling to take folic acid or vitamin B12 supplementation; Is unable to
take corticosteroids; (Apply to cohort 1)
10. Has the following conditions in physical examination and laboratory examination:
With a known positive history of human immunodeficiency virus (HIV), Has known history
of Human Immunodeficiency Virus (HIV) positive or acquired immunodeficiency syndrome
(AIDS); Subjects with positive for treponema pallidum (TP) antibody; With active
hepatitis, hepatitis B: HBsAg positive and/or HBcAb positive,a nd HBV-DNA level
positive or above the ULN; hepatitis C: HCV antibody positive and HCV-RNA level
positive or above the ULN;
11. Has a known contraindications or history of hypersensitivity to any component of test
drug or to any excipients.
12. Has received organ in the past or autologous stem cell transplantation within 3 months
before the first dose.
13. Received radiation therapy to the lung in the past.
14. Has other history of malignancy within the past 3 years, except locally curable cancer
(such as radical melanoma, basal or squamous cell carcinoma, in situ cancer of the
bladder or cervix).
15. Has received any drugs with anti-cancer indications (including Chinese herbal or
patent medicine, immunosuppressants, systemic or topical hormones) for
immunosuppression within 14 days before the first dose (Daily dose of systemic
corticosteroid equivalent to prednisone >10 mg).
16. Had major surgery (<28 days prior to first dose) or have not recovered from major
surgery.
17. Has active autoimmune disease that has required systemic treatment in past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
18. Patients with unexplained fever > 38.5°C during the screening period and before the
first dose (judged by the investigator, patients with fever due to tumors can be
enrolled).
19. Received any other study therapy (drugs or devices) within 4 weeks prior to first
dose.
20. Had a history of substance abuse or alcoholism (<6 months prior to first dose).
21. Have received a live-virus vaccination within 28 days prior to the first dose or plan
to receive a live-virus vaccination during the study (Inactivated virus vaccines such
as injectable seasonal flu vaccine and COVID-19 vaccine are allowed during the study
period).
22. Is pregnant or breastfeeding; Female of childbearing potential or male with a female
partner(s) of child-bearing potential is unwillingness to use effective contraception
measures during the study or through 6 months after last dose.
23. The investigator believes that it is not suitable for enrollment.
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