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.
Single group
JS207
DrugJS207 (10 mg/kg or 15 mg/kg, IV, d1)
Pemetrexed
DrugPemetrexed (500 mg/m², IV, d1)
Carboplatin or cisplatin
DrugPlatinum-based chemotherapy (carboplatin: AUC5, d1 or cisplatin 75 mg/m², d1) every 3 weeks (Q3W) for a total of 4 cycles
JS212
DrugJS212(4.2mg/Kg or Other dose， IV, d1）
Investigator-assessed objective response rate (ORR)
Evaluate the investigator-assessed objective response rate (ORR) of JS207 combined withTherapies in the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) patients with positive driver genes and who have failed tyrosine kinase inhibitor (TKI) therapy.The ORR is defined as the proportion of subjects who have a partial response (PR) or a complete response (CR) in the Best Overall Response.
Investigator-assessed objective response rate (DCR)
The DCR is defined as the proportion of subjects whose Best Overall Response (BOR) is Complete Response (CR), Partial Response (PR), or Stable Disease (SD)
Investigator-assessed Duration of Response (DoR)
The DoR is defined as the time from the first occurrence of CR or PR to the first occurrence of Progressive Disease (PD) or death (whichever occurs first). The DoR is only applicable to subjects whose BOR is CR or PR
Investigator-assessed Progression-Free Survival (PFS)
The PFS is defined as the time from the first administration of the drug to the first documented disease progression (PD) according to the RECIST v1.1 criteria or death due to any disease (whichever occurs first)
Investigator-assessed overall survival (OS)
The OS is defined as the time from the first administration of the drug to death due to any cause
the trough concentrations (PK)
To characterize the trough concentrations of JS207
Immunogenicity(ADA)
The immunogenicity of JS207, including the titer of ADA
Immunogenicity(NAb)
The immunogenicity of JS207, including the incidence rate of neutralizing antibodies (NAb) (if applicable)
Expression level of PD-L1 in tumor tissues
The correlation between the expression level of PD-L1 in tumor tissues and the therapeutic effect
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