| Eligibility |
Inclusion Criteria:
1. Sign written informed consent before any trial-related processes are implemented;
2. Age = 18 years old and = 75 years old;
3. Life expectancy exceeds 3 months;
4. The investigator confirmed at least one measurable lesion according to the RECIST 1.1
standard. A measurable lesion located in the field of previous radiation therapy or
after local treatment may be selected as a target lesion if it is confirmed to have
progressed;
5. Patients with treated metastatic or recurrent (stage IV) NSCLC confirmed by histology
or cytology according to the International Association for the Study of Lung Cancer
and the American Association for the Classification of Cancer Classification, 8th
edition;
6. The Eastern Cancer Cooperative Group (ECOG) has a fitness status score of 0 or 1;
7. Patients with genetic testing (allowing PCR and NGS detection methods) confirmed
uncommon mutations (EGFR G719X, L861Q, S768I, and 20ins et al.), patients can accept
two or more types of EGFR rare co-mutation. Populations with the primary EGFR T790M
mutation can also be included in the study.
8. Patients who have experienced disease progression after at least two treatment
regimens for advanced/metastatic disease must include a platinum-containing systemic
chemotherapy and an EGFR-TKI treatment. Patients with EGFR 20ins who have experienced
disease progression only after platinum-containing systemic chemotherapy.
9. Hematological function is sufficient, defined as absolute neutrophil count =1.5×109
/L, platelet count =100 ×109 /L, hemoglobin =90g/L (no history of blood transfusion
within 7 days);
10. Hepatic function is adequate, defined as all patients with total bilirubin levels =
1.5 times normal upper limit (ULN) and aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) levels = 2.5 times ULN, or for patients with liver metastases ,
AST and ALT levels = 5 times ULN;
11. adequate renal function, defined as creatinine clearance = 45 ml/min (Cockcroft-Gault
formula);
12. Coagulation function is adequate, defined as international normalized ratio (INR) or
prothrombin time (PT) = 1.5 times ULN; if the subject is receiving anticoagulant
therapy, as long as the INR or PT is within the range of anticoagulant drugs can;
13. Female subjects of childbearing age should be negative for urine or serum pregnancy
test within 3 days prior to receiving the first study drug. If the urine pregnancy
test result cannot be confirmed as negative, a blood pregnancy test is required;
14. If there is a risk of conception, male and female patients need to use high-efficiency
contraception (ie, an annual failure rate of less than 1%) and continue until at least
180 days after stopping the trial treatment; Note: If abstinence is normal for the
subject Lifestyle and preferred methods of contraception can be used as a method of
contraception.
Exclusion Criteria:
1. Histology is NSCLC, if there are small cell carcinoma, neuroendocrine carcinoma,
sarcoma components, it can not be included;
2. Patients with known EGFR-sensitive mutations (19-Del and L858R);
3. Cavity lung squamous cell carcinoma, or non-small cell lung cancer patients with
hemoptysis (>50 mL/day);
4. Patients whose tumor has invaded an important blood vessel or who is judged by the
investigator to have major bleeding during the follow-up study;
5. Patients with any signs or history of bleeding physique;
6. Currently participating in interventional clinical research treatment, or receiving
other research drugs or research equipment within 4 weeks prior to the first dose;
7. Previously received the following treatments: anti-PD-1, anti-PD-L1 or anti-PD-L2
drugs or against another stimulus or synergistic inhibition of T cell receptors (eg
CTLA-4, OX-40, CD137) drug;
8. Received a proprietary Chinese medicine or immunomodulatory drug (thymosin,
interferon, interleukin, etc.) with anti-cancer indications within 2 weeks before the
first dose, or received major surgery within 3 weeks before the first dose;
9. Received a physical organ or blood system transplant;
10. There is clinically uncontrollable pleural effusion/peritoneal effusion (patients who
do not need drainage or stop drainage and have no significant increase in 3 days of
effusion can be enrolled);
11. The tumor compresses important organs (such as the esophagus) around it and is
accompanied by related symptoms, oppression of the superior vena cava or invasion of
the mediastinal vessels, heart, etc.;
12. Class III-IV congestive heart failure (New York Heart Association classification),
poorly controlled and clinically significant arrhythmias;
13. Any arterial thrombosis, embolism or ischemia occurred within 6 months prior to
enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident
or transient ischemic attack. A history of deep vein thrombosis, pulmonary embolism,
or any other severe thromboembolism within 3 months prior to enrollment (implanted IV
port or catheter-derived thrombosis, or superficial vein thrombosis is not considered
a "serious" thrombosis embolism);
14. It is known that there is an allergic reaction to the active ingredient of sindril mAb
and or any excipients;
15. Active autoimmune diseases requiring systemic treatment (eg, using disease-modifying
drugs, corticosteroids or immunosuppressants) within 2 years prior to the first dose.
Alternative therapies (such as thyroxine, insulin, or physiological doses of
corticosteroids for adrenal or pituitary insufficiency) are not considered systemic
treatments;
16. Patients who require long-term systemic use of corticosteroids. Patients with
intermittent use of bronchodilators, inhaled corticosteroids, or topical
corticosteroids due to COPD or asthma may be enrolled.
17. has not fully recovered from toxicity and/or complications caused by any intervention
prior to initiation of treatment (ie, =1 or baseline, excluding fatigue or alopecia);
18. diagnosis within 5 years prior to initial dosing For other malignancies, it does not
include radical cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma,
and/or radically resected carcinoma in situ. If more than 5 years before the drug is
diagnosed as other malignant tumors or lung cancer, pathological or cytological
diagnosis of recurrent metastatic lesions is required;
19. symptomatic central nervous system metastasis. For patients with asymptomatic brain
metastases or brain metastases with stable symptoms after treatment, as long as all
the following criteria are met, participate in this study: measurable lesions outside
the central nervous system; no midbrain, pons, cerebellum, meninges, Medulla or spinal
cord metastasis; maintain clinical stability for at least 2 weeks; stop hormone
therapy 14 days before the first study drug;
20. One year before the first dose, a history of non-infectious pneumonia requiring
corticosteroid treatment or the presence of non-infectious pneumonia;
21. active infections requiring treatment or systemic anti-infectives used within one week
prior to first administration;
22. There are known cases of mental illness or substance abuse that may have an impact on
compliance with the test requirements;
23. A history of human immunodeficiency virus (HIV) infection (ie, HIV 1/2 antibody
positive), known syphilis infection (positive syphilis antibody), and active
tuberculosis are known.
24. Untreated active hepatitis B; Note: Hepatitis B subjects meeting the following
criteria are also eligible for inclusion:
The HBV viral load must be <1000 copies/ml (200 IU/ml) or below the lower limit of
detection before the first dose. Subjects should receive anti-HBV treatment during the
entire study chemotherapy drug treatment to avoid viral reactivation. For subjects
with anti-HBc(+), HBsAg(-), anti-HBs(-), and HBV viral load (-), prophylactic anti-HBV
therapy is not required, but viral reactivation is closely monitored;
25. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower
limit of detection);
26. Vaccination with live vaccine within 30 days prior to first dose; Note: Injectable
inactivated virus vaccine for seasonal influenza is permitted; however, live
attenuated influenza vaccine for intranasal administration is not permitted;
27. There are medical history, disease, treatment, or laboratory abnormalities that may
interfere with the test results, hinder the subject's full participation in the study,
or the investigator believes that participating in the study is not in the best
interest of the subject.
28. Local or systemic diseases caused by non-malignant tumors, or secondary reactions to
cancer, and may lead to higher medical risks and/or uncertainty in survival
assessment.
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