TKI Tedavisi Başarısız Olan Sürücü Gen Pozitif İleri Evre Küçük Hücreli Dışı Akciğer Kanseri Hastalarında JS207 (PD-1/VEGF Bispesifik Antikor) Kombinasyon Tedavilerinin Faz II Çalışması

Inclusion Criteria:

1. Age between 18 and 75 years old (both 18 and 75 years old included) at the time of signing the informed consent form, applicable to both males and females.
2. Locally advanced (stage IIIB/IIIC), metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) confirmed by histology or cytology, which is not eligible for radical surgery or radical chemoradiotherapy.
3. Positive for driver genes, including but not limited to any of the following: EGFR sensitive mutations (18 exon G719X mutation, 19 exon deletion mutation, 20 exon S768I or T790M mutation, 21 exon L858R or L861Q mutation), ALK fusion, ROS1 fusion, BRAF V600E mutation, NTRK fusion, MET14 exon skipping mutation, RET fusion, KRAS G12C mutation, HER-2 mutation, EGFR 20 exon insertion mutation.
4. Previous targeted therapy failed and there is currently no standard targeted treatment available.
5. Cohort1: PD-L1 positive (TPS ≥ 1%) confirmed by the central laboratory or the research center. Cohort2:: Organized samples must be provided for the central laboratory to conduct retrospective biomarker testing (which may include PD-L1, EGFR and HER3 expression).
6. Being able to provide a qualified test report for positive driver gene, or agreeing to provide a qualified sample for driver gene testing.
7. According to the RECIST v1.1 criteria, the subject has at least 1 measurable lesion.
8. Performance status score of 0-1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
9. Expected survival period ≥ 12 weeks.
10. The function of important organs meets the requirements of the protocol.
11. For female subjects with reproductive capacity who have sexual relations with unsterilized male partners, they must agree to have no pregnancy plans and to take effective contraceptive measures during the period from signing the ICF to 7 months after the last administration of JS212, or 6 months after the last administration of JS207 or chemotherapy drugs (whichever is the longer period of contraceptive requirement). For unsterilized male subjects who maintain sexual relations with female partners with reproductive capacity, they must agree to take effective contraceptive measures during the period from signing the ICF to 4 months after the last administration of JS212, or 6 months after the last administration of JS207 or chemotherapy drugs (whichever is the longer period of contraceptive requirement) (Appendix 4). For female patients with reproductive capacity, the HCG test in the 7 days prior to study enrollment must be negative and they must be non-lactating.
12. Voluntarily joining this study, signing the informed consent form, having good compliance, and cooperating with the follow-up.

Exclusion Criteria:

1. Diseases accompanied by those listed in the protocol, including those with histopathological or cytopathological confirmation of the tumor combined with neuroendocrine tumor (including small cell lung cancer, large cell neuroendocrine carcinoma, etc.) components, or with the squamous cell carcinoma component exceeding 10%; known meningeal metastasis; symptomatic brain metastasis; the tumor encircling important blood vessels or with obvious necrosis and cavities, and the investigator deems that it may pose a risk of bleeding, etc.
2. Received the treatments listed in the plan, including immune-mediated treatments; systemic chemotherapy, anti-VEGF pathway target drugs, anti-EGFR and/or HER3 target drugs, and ADC drugs containing topoisomerase inhibitors (only applicable to cohort 2).
3. Having an obvious bleeding tendency or a history of severe coagulation dysfunction.
4. Gastrointestinal perforation, intra-abdominal fistula or intra-abdominal abscess occurred within 6 months before the first administration, or currently having high-risk factors for perforation/fistula formation of the hollow viscus as judged by the investigator.
5. Having a serious, unhealed or ruptured wound, active ulcer or untreated fracture.
6. Having uncontrolled hypertension, or a history of hypertensive crisis or hypertensive encephalopathy.
7. Expected that the toxicity of previous anti-tumor treatment has not recovered to ≤ grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE).
8. Known allergy to the investigational drug or its excipients, pemetrexed, platinum drugs (carboplatin/cisplatin), or known history of ≥ grade 3 allergy to antibody drugs in the past.
9. Having an active autoimmune disease or a history of autoimmune disease.
10. Having a history of immunodeficiency.
11. Having a severe infection within 4 weeks before the first use of the investigational drug.
12. History of confirmed or suspected interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced pneumonia, idiopathic pneumonia, or other moderate to severe lung diseases that seriously affect lung function.
13. Active pulmonary tuberculosis infection detected by medical history or CT examination.
14. Having active tuberculosis, hepatitis B, or hepatitis C.
15. Having been diagnosed with any other malignant tumor within 5 years before the first use of the investigational drug.
16. Uncontrolled concurrent diseases listed in the protocol.
17. As judged by the investigator, having other severe, acute or chronic medical diseases, mental diseases or laboratory abnormalities that may increase the risk associated with participating in the study, or may interfere with the interpretation of the study results. "