| Eligibility |
Inclusion Criteria:
- 1. Age>=18 years, both men and women can be enrolled 2. Histologically confirmed
adenocarcinoma (does not contain small cell components).
3. Locally advanced, untreated recurrent or metastatic lung adenocarcinoma not
suitable for radical surgery or radiotherapy. Previous neoadjuvant and adjuvant
radiochemotherapy can be accepted (chemotherapy/radiotherapy, non-immunotherapy),
tumor progression =6 months before the end of neoadjuvant / adjuvant therapy is
required .
4. ECOG score of physical condition was 0-1, and there was no deterioration in the
first 2 weeks. Expected survival over 12 weeks.
5. According to the RECIST1.1 criteria, it is required that at least one measurable
treatment naive lesion (has not been treated with radiotherapy in the past and will
not receive local therapy such as radiotherapy throughout the treatment); If the
lesion has been treated with radiotherapy then the progress of this lesion need to be
confirmed by imaging, before being used as the target lesion.
6. Laboratory certified by CAP reported negative in EGFR and ALK mutation-sensitive
mutations.
7. Clinical laboratory examination indicators meet the following standards:
1. Platelet =100×109/L
2. Absolute neutrophil count (ANC) =1.5×109/L, or absolute white blood cell count
(WBC) =3.5×109/L
3. Hemoglobin (Hgb) = 100 g/L (without blood transfusion or erythropoietin use
within 4 weeks)
4. Total bilirubin = 1.5 times the upper limit of normal value (ULN) (If there is
liver metastasis, allow =2.5 times ULN)
5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 times
ULN
6. Creatinine =1.5 times ULN or Creatinine clearance =50 mL/min (Calculated
according to the Cockcroft Gault formula)
7. Serum amylase = 2 times ULN or pancreatic amylase = 1.5 times ULN
8. Serum lipase = 1.5 times ULN
9. patients who did not take anticoagulants, or those who had previously used
anticoagulants, had been discontinued for 28 days before enrollment, and the
international normalized ratio (INR) = 1.5 and activated partial thromboplastin
time (APTT) = 1.5 times ULN.
8. Able to swallow oral medication. 9. Enough tissue specimens for PD-L1
detection or exploratory analysis.
Exclusion Criteria:
- 1.The histological component of NSCLC containing small cell lung cancer or squamous
cell carcinoma was excluded.
2. Previously untreated or symptomatic central nervous system (CNS) metastases or
meningeal diseases, spinal cord compression, meningeal metastases and brain metastases
with obvious symptoms, etc. For those who have received radiotherapy and/or surgery,
patients with no evidence of CNS disease progression = 2 weeks after the end of
treatment, patients who had not been treated with corticosteroids for more than 2
weeks before the start of treatment were eligible.
3. Clinically significant hemoptysis (at least 0.5 teaspoons of fresh blood) or tumor
bleeding occurred within 2 weeks before the first dose of study treatment.
4. There is imaging evidence of invasion/infiltration of large vessels. Due to the
potential risk of severe bleeding associated with tumor shrinkage/necrosis after
apatinib treatment, the degree of tumor invasion/infiltration of major blood vessels
should be considered.
5. Cancerous thrombus with clinical significance, and the use of anticoagulant drugs
within 28 days before enrollment.
6. Clinically uncontrollable pleural effusion/abdominal effusion. 7. Glucocorticoid
treatment 28 days before the first dose (equivalent dose of >10 mg prednisone per
day).
8. Having active autoimmune diseases, which require systemic treatment in the past 2
years (ie using disease-modifying drugs, corticosteroids or immunosuppressive drugs).
Replacement therapy (for example, thyroxine, insulin, or physiological corticosteroid
replacement therapy due to adrenal or pituitary insufficiency, etc.) is not considered
as systemic therapy and is allowed.
9. History of other malignant tumors in the past 5 years. 10. Has received previous
systemic chemotherapy or other targeted or biological anti-tumor treatment for its
metastatic NSCLC (As long as treatment is completed at least 6 months before diagnosis
of metastatic NSCLC, prior chemotherapy and/or radiotherapy is allowed as part of
neoadjuvant/adjuvant therapy for non-metastatic NSCLC).
11. Previously received anti-PD-1, anti-PD-L1, anti-PD-L2 and other drugs or drugs
acting on another stimulatory or co-suppressive T cell receptor (eg CTLA-4, OX 40,
CD137 ) therapy, or cell biological therapy, etc.
12. Previously received treatment with apatinib, or received systemic medication with
a clear anti-tumor mechanism.
13. Allogeneic tissue/solid organ transplantation has been performed. 14. In addition
to hair loss and stable peripheral neurotoxicity below grade 2, any clinical toxicity
associated with prior treatment before enrollment did not return to pre-treatment
levels or grade 1.
15. pregnancy status (positive blood HCG) and lactation. 16. Previously suffering from
interstitial lung disease, drug-induced interstitial lung disease, radiation
pneumonitis requiring hormone therapy, or any active interstitial lung disease with
clinical evidence.
17. Known liver diseases of clinical significance, including active viral hepatitis,
alcoholic hepatitis or other hepatitis, liver cirrhosis, hereditary liver disease.(
patients who have been cured of previous HBV infection (defined as hepatitis B core
antibody [HBcAb] positive and HBsAg negative) can participate in this study. Before
entering the group, HBV DNA testing must be performed on this class of patients and
well-controlled hepatitis B (peripheral HBV DNA testing is less than 103/ml) can be
considered for this experiment, and antiviral treatment should be given. Previous
patients infected with hepatitis C virus (HCV) had positive HCV antibody test results,
They were eligible for this study only if the HCV RNA polymerase chain reaction test
result was negative (below the detection limit).) 18. Patients who are suspected or
have demonstrated an impaired immune function or infection, including:
- Evidence that active or latent tuberculosis (TB) is determined by locally
approved screening methods. If the screening results require treatment in
accordance with local treatment guidelines or clinical practice, the patient is
disqualified.
- Chronic or active hepatitis B or hepatitis C.
- Known history of human immunodeficiency virus (HIV) infection. During the
screening period, the local test result was positive.
- There are any other medical conditions (such as active infections that have been
treated or not treated) that the investigator believes that the patient has an
unacceptable risk if receiving immunomodulatory therapy(Patients with local
diseases that are unlikely to cause systemic infections (such as chronic nail
fungal infections) are allowed to be enrolled).
19. Allogeneic bone marrow or organ transplantation. 20. Any immunomodulator with
systemic effects. 21. Known mental illness or substance abuse disorders that
interfere with a subject's ability to comply with research requirements.
22. Previous severe allergy to mAb treatment or known allergy or intolerance to
any component of study medication (apatinib, caririzumab).
|
