JS001 Combination Therapy in NSCLC Negative Driving Gene After First-line Chemotherapy.

A Single-arm, Single-center, Phase II Clinical Study to Investigate the Efficacy and Safety of JS001 Combined With Axitinib in the Treatment of Advanced Non-small Cell Lung Cancer (NSCLC) With Negative Driving Gene After First-line Chemotherapy

This is a phase II, open, single-center clinical study to evaluate the efficacy and safety of JS001 combined with Axitinib in the treatment of advanced non-small cell lung cancer without activated EGFR mutation, ALK fusion and ROS fusion after or during first-line chemotherapy. About 50 subjects will be included in this study and will be treated with JS001 combined with acitinib. Each cycle is 21 days.

Inclusion Criteria:

1. Signed the informed consent form (ICF);
2. Recurrent or advanced stage Ⅲ B or IV non-small cell lung cancer tested for EGFR mutation and ALK, ROS1 fusion gene, and all the driving gene was negative.
3. At least one measurable lesion (according to RECIST 1.1);
4. Failure of previous first-line standard chemotherapy:
5. Patients who agreed to provide previously stored tumor tissue specimens or fresh biopsies of tumor lesions
6. Age 18-75 years old, regardless of gender;
7. ECOG score 0-1;
8. Expected survival time ≥ 3 months;
9. Laboratory test value must show enough organ function

Exclusion Criteria:

1. Tumor histology or cytological pathology confirmed the presence of small cell lung cancer components, or sarcomatoid lesions;
2. Those who did not have a driving gene test;
3. Investigator believed that there was a clear bleeding tendency
4. Subjects who are currently participating in and receiving treatment in other studies, less than 4 weeks
5. Patients who had previously received second-line or more systemic chemotherapy for advanced NSCLC;
6. Patients who had received hematopoietic stimulating factors, within one week before the start of the study.
7. Uncontrollable or symptomatic hypercalcemia
8. Within 6 months before receiving the study treatment, they received chest (lung) radiotherapy > 30Gy, or received radiotherapy within 4 weeks or radiopharmaceuticals within 8 weeks, except for local palliative radiotherapy for bone metastases.
9. The adverse reactions of previous antineoplastic therapy have not yet recovered to CTCAE 5.0 grade ≤ 1 (except alopecia);
10. Major surgery or radiotherapy has been performed within 4 weeks before joining the group or has not yet fully recovered from the previous operation
11. Known active central nervous system (CNS) metastasis and / or cancerous meningitis;
12. Spinal cord compression without radical treatment of surgery and / or radiotherapy;
13. Uncontrolled tumor-related pain;
14. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage ;
15. Evidence of active pneumonia was found;
16. Clinically uncontrolled active infections;
17. Uncontrollable major seizures or superior vena cava syndrome;
18. Past or present co-existence of other malignant tumors;
19. Liver diseases known to be of clinical significance;
20. Those who have previously used any anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-CTLA-4 antibody and Axitinib;
21. Patients with active tuberculosis (TB);
22. Patients with any active autoimmune disease or history of autoimmune disease;
23. Any anti-infective vaccine;
24. Known (HIV) infection of human immunodeficiency virus;
25. The researchers believe that it can affect study compliance;
26. Patients who received systemic immunosuppressive drugs within the first 4 weeks of the first day of the first cycle;
27. History of severe allergy, anaphylaxis or other hypersensitivity to chimeric or humanized antibodies or fusion proteins;
28. Those who are known to be allergic to biological drugs;
29. Those who are known to be allergic to acitinib;
30. Patients with a history of arterial or venous thromboembolism;
31. Known hereditary or acquired bleeding and thrombotic tendencies;
32. Patients who have previously received allogeneic stem cell or parenchyma organ transplantation;
33. Pregnant or lactating women or women of childbearing age who were positive for serum pregnancy test before taking the drug for the first time