Efficacy and Safety of Neoantigen Peptide Vaccine in the Treatment of Advanced NSCLC Progressed After EGFR-TKI Treatment

Inclusion Criteria:

1. The patient voluntarily joined this study and signed an informed consent form;
2. ≥ 18 years old, both male and female;
3. Pathologically confirmed IIIB-IV stage NSCLC, with at least one measurable lesion thathas not undergone local treatment (according to RECIST v1.1, the length of themeasurable lesion on spiral CT or MRI scans is ≥ 10 mm or the short diameter of theenlarged lymph node is ≥ 15 mm);
4. Metastatic advanced EGFR mutated lung cancer confirmed by histology or cytology, withEGFR-TKI monotherapy or EGFR-TKI combined anti angiogenic therapy failing;
5. Patients who have received first-line chemotherapy in the past can be included in theinclusion criteria;
6. ECOG score: 0-2;
7. Expected survival time ≥ 12 weeks;
8. The functions of important organs meet the following requirements:Absolute neutrophilcount ≥ 1.5 × 109/L;Absolute lymphocyte count ≥ 0.8 × 109/L;Platelets ≥ 80 × 109/L;Hemoglobin ≥ 90g/L;Bilirubin ≤ 1.5 × ULN (within 7 days before the firstmedication);ALT and AST ≤ 1.5 × ULN (within 7 days before the first medication); Serumcreatinine ≤ 1.5 × ULN;
9. Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 and FT4 levels should beexamined simultaneously, and if FT3 and FT4 levels are normal, they can be included inthe group level);
10. For female patients of childbearing age, effective methods of contraception should beused during the trial period and within 3 months after the last administration oftreatment medication;
11. Agree to provide blood samples and histological specimens.

Exclusion Criteria:

1. The patient has any active autoimmune disease or a history of autoimmune disease;
2. The patient is currently using immunosuppressive agents or systemic hormone therapy toachieve immunosuppressive effects (dosage>10mg/day of prednisone or other therapeutichormones) ;
3. The patient experienced severe allergic reactions to other monoclonal antibodies;
4. Suffering from hypertension and unable to achieve good control throughantihypertensive medication treatment (systolic blood pressure ≥ 140mmHg or diastolicblood pressure ≥ 90mmHg);
5. There are clinical symptoms or diseases of the heart that cannot be well controlled,such as:NYHA grade 2 or above heart failure;Unstable angina pectoris; Have experiencedmyocardial infarction within 1 year;Clinically significant supraventricular orventricular arrhythmias require treatment or intervention; QTc>450ms (male); QTc>470ms (female);
6. Abnormal coagulation function (INR>2.0, PT>16s), with bleeding tendency or undergoingthrombolysis or anticoagulation treatment, allowing prophylactic use of low-doseaspirin and low molecular weight heparin;
7. Received previous anti-tumor immunotherapy and anti-tumor vaccine treatment;
8. The patient has active infection, unexplained fever ≥ 38.5 ° C within 7 days beforemedication, or baseline white blood cell count>15 × 109/L; Those who may have purulentor chronic infections, and the wound persists without healing;
9. Patients who have experienced bone metastasis have received palliative radiotherapy inareas greater than 5% of the bone marrow area within the 4 weeks prior toparticipating in this study;
10. The patient has previously received anti PD-1, anti PD-L1, and anti PD-L2 treatment;
11. Those who are known to be allergic to the components of recombinant humanizedanti-PD-1 monoclonal antibody drugs and vaccines;
12. Pregnant or lactating women, or female patients with fertility who have not takencontraceptive measures;
13. Other malignant tumors (excluding basal cell or squamous cell carcinoma, superficialbladder cancer cancer, cervical carcinoma in situ or breast cancer) in the past 5years;
14. Patients who participate in other clinical trials at the same time;
15. HIV positive; HCV positive; Uncontrolled active hepatitis B;
16. Those who have received live vaccination within 4 weeks before the start of treatment;
17. Patients with a history of asymptomatic brain metastasis who meet all the followingconditions can be selected:During screening, brain imaging showed no evidence ofimmediate progression.There is currently no need to use glucocorticoids to treat brainmetastases, and stable doses of anticonvulsants are allowed.