| Eligibility |
Inclusion Criteria:
- 1. Age: 18-75 years old; 2. ECOG physical status: 0-1; 3. The expected survival time
is more than 3 months; 4. Patients with locally advanced/unresectable stage IIIA-C
NSCLC confirmed by histopathology or cytology based on the AJCC 8th edition staging
system at initial diagnosis 5. Did not receive any anti-tumor treatment; 6. No known
sensitive EGFR/ALK/ROS1 mutations 7. According to RECIST criteria, at least one
measurable lesion must be used as the target lesion 8. Good organ function = 7 days
before the first dose of study drug, as indicated by the following laboratory values:
1. Absolute neutrophil count (ANC) =1.5 x 109/L, platelet =100 x 109/L, hemoglobin
=90g/L;
2. INR or PT =1.5 x ULN;
3. aPTT =1.5 x ULN;
4. Total serum bilirubin =1.5 x ULN;
5. AST and ALT = 2.5x ULN or =5×ULN in patients with liver metastases;
6. albumin =25 g/L (2.5 g/dL);
7. Serum creatinine =1.5 times the upper limit of normal value (ULN), or serum
creatinine clearance calculated by Cockcroft-Gault formula >50 mL/min; 9.
Informed consent signed by patients or their legal representatives was obtained,
and the study protocol and follow-up procedure were followed.
10. Patients of childbearing potential had to be willing to continue using
high-potency contraception for the duration of the study and for =120 days after
the last dose of Cadonilimab (AK104).
Exclusion Criteria:
1. Pathological types of mixed small cell and non-small cell lung cancer;
Patients with known EGFR/ALK/ROS1 mutations; 2. 3. Patients have received an
approved systemic anticancer therapy or systemic immunomodulatory agent
(including, but not limited to, interferon, interleukin-2, and tumor necrosis
factor) within 4 weeks before the first dose; 4. Have received a live or
attenuated live vaccine within 4 weeks before enrollment or are expected to
require a live or attenuated live vaccine during the study or within 5 months
after the last dose of Cadonilimab (AK104); 5. Patients allergic to
Cadonilimab(AK104) or any of the ingredients, or the container; 6. Untreated
patients with chronic hepatitis B or chronic hepatitis B virus carriers with HBV
DNA=500 IU/mL or patients with active hepatitis C: Patients with inactive HBsAg
carriers and medically stable active HBV infection (HBV DNA<500 IU/mL) were
eligible. Only to hepatitis b core antibody (anti HBc antibody) patients who
tested positive for HBV DNA testing.
Patients who were negative for hepatitis C virus (HCV) antibodies at screening or
who were positive for HCV antibodies at screening and subsequently tested
negative for HCV RNA were eligible. HCV RNA testing will be performed only in
patients who are positive for hepatitis C virus (HCV) antibodies.
Note: the hepatitis b surface antigen (HBsAg) can be detected or patients with
HBV DNA can be detected, should according to the guidelines for treatment.
Patients receiving antiviral treatment at screening were supposed to have been on
treatment for more than 2 weeks before enrollment and to have continued treatment
for 6 months after discontinuation of the study drug.
7. Need systemic treatment of active autoimmune disease, the researchers reckon
have an impact on research and treatment of patients; 8. Any condition requiring
systemic treatment with a corticosteroid (prednisone or equivalent >10 mg/ day)
or other immunosuppressive agent, within 14 days before the first dose of the
study drug, that was assessed by the investigator as having an impact on the
study treatment; 9. Severe chronic or active infection (including tuberculosis
infection, etc.) requiring antimicrobial, antifungal, or antiviral systemic
therapy within 14 days prior to the first dose of study drug 10. Always
allogeneic stem cell transplantation or organ transplantation; 11. Meet the
following any kind of cardiovascular risk factors of standard:
1. Cardiogenic chest pain =28 days before the first dose of study drug, defined as
moderate pain that limits instrumental exercise of daily living;
2. Symptomatic pulmonary embolism =28 days before the first dose of study drug;
3. Any history of acute myocardial infarction =6 months before the first dose of
study drug;
4. Any history of New York Heart Association (NYHA) class III or IV heart failure =6
months before the first dose of study drug;
5. Any ventricular arrhythmic event of grade =2 occurred =6 months before the first
dose of study drug.
6. History of any cerebrovascular accident =6 months before the first dose of study
drug;
7. Corrected QT interval (QTc) (corrected with Fridericia's method) >450 msec; Note:
If the QTc interval on the initial ECG was >450 ms, a subsequent ECG was
performed to rule out the result
8. Left ventricular ejection fraction (LVEF) = the lower limit of normal (LLN) as
assessed by echocardiography (ECHO);
9. Any syncope or seizure occurring =28 days before the first dose of study drug;
12. Patients with uncontrolled hypertension (defined as systolic blood pressure >
150 mmHg and/or diastolic blood pressure > 100 mmHg); 13. Bleeding, thrombotic
disorders, or use of an anticoagulant (e.g., warfarin) or similar medication
requiring therapeutic INR monitoring within 6 months before the first dose of a
study drug that, in the investigator's judgment, may have influenced treatment;
14. Patients with any sign or history of bleeding that was assessed by the
investigator as having an impact on the study protocol; Patients who had any
bleeding event of grade 3 or higher, nonhealed wound, ulcer, or fracture within 4
weeks before the first dose; 15. Hemoptysis > 50ml/d; 16. The central cavity or
tumor was shown to invade or be adjacent to large vessels by imaging studies, and
the tumor was assessed by the investigator as likely to invade large vessels and
cause fatal bleeding.
17. Unable to swallow capsules or significant influence disease or a history of
gastrointestinal function, such as malabsorption syndrome, stomach or intestinal
resection, bariatric surgery, with symptoms of inflammatory bowel disease, or
incomplete or complete intestinal obstruction.
18. Patients requiring treatment with gastric ph-regulating drugs, including
proton pump inhibitors and/or H2 antagonist drugs. Patients can convert antacids;
19. Patients with a history of uncontrolled systemic diseases, including diabetes
mellitus, hypertension, pulmonary fibrosis, or acute lung disease, that were
assessed by the investigator as having an impact on the study treatment; 20.
Patients with a history of major illness or clinical manifestations that may
affect the function of organ systems and are considered by the investigator to
have an impact on the study treatment; 21. Had undergone any major surgery
requiring general anesthesia within 28 days or less before the first dose; 22.
There are underlying medical conditions or alcohol/drug abuse or dependence that
contraindicate the use of the experimental drug or preclude the administration of
the study drug, or may affect the interpretation of the results, or place the
patient at a high risk of treatment complications; 23. Known human
immunodeficiency virus (HIV) infection; 24. Any activity before the group 2 years
or less malignant tumor, except in the study of the specific cancer and any local
recurrence has been cured of cancer (such as removal of basal cell or squamous
cell cancer, superficial bladder cancer, cervical or breast carcinoma in situ);
25. Pregnant or lactating women, or male and female patients who plan to have a
child during the study period; 26. Participate in another therapeutic clinical
study at the same time, unless it is an observational (nonintervention) clinical
study or is in the follow-up period of an intervention study.
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