This study targets patients with advanced NSCLC driven with positive driver genes who have failed TKI treatment, enrolling 66-78 participants. Cohort1 ：Patients will receive JS207 (10 or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin Area Under the Curve(AUC)5 or cisplatin 75 mg/m², d1) every 3 weeks for 4 cycles. Afterward, JS207 and pemetrexed will continue as maintenance therapy until discontinuation criteria are met. Cohort2 ：The treatment received was JS207 (10mg/kg, intravenous, on day 1) + JS212 (4.2mg/kg or another SMC-selected dose, intravenous, on day 1), every 3 weeks, until the termination criteria were met. The study aims to assess the safety, tolerability, and preliminary efficacy of JS207 combination therapy.
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.
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.
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.
Previous targeted therapy failed and there is currently no standard targeted treatment available.
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.
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).
Having an obvious bleeding tendency or a history of severe coagulation dysfunction.
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.