Non-squamous Non-small Cell Lung Cancer
Conditions
Brief summary
This study targets patients with advanced NSCLC driven with positive driver genes who have failed TKI treatment, enrolling 36-42 participants. Patients will receive JS207 (10 or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin AUC5 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. The study aims to assess the safety, tolerability, and preliminary efficacy of JS207 combination therapy.
Detailed description
This study enrolls patients with advanced non-small cell lung cancer (NSCLC) who have positive driver genes and have failed TKI treatment. Approximately 36-42 patients are expected to be enrolled and receive treatment with JS207 (10 mg/kg or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin: AUC5, d1 or cisplatin 75 mg/m², d1) every 3 weeks (Q3W) for a total of 4 cycles.After the 4 cycles, patients will continue receiving JS207 (10 mg/kg or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) every 3 weeks (Q3W) until they meet the criteria for treatment discontinuation.The study aims to evaluate the safety, tolerability, and preliminary efficacy of JS207 in combination with pemetrexed and platinum-based chemotherapy.
Interventions
DRUGJS207
JS207 (10 mg/kg or 15 mg/kg, IV, d1)
DRUGPemetrexed
Pemetrexed (500 mg/m², IV, d1)
Platinum-based chemotherapy (carboplatin: AUC5, d1 or cisplatin 75 mg/m², d1) every 3 weeks (Q3W) for a total of 4 cycles
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
JS207 (10 mg/kg or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin: AUC5, d1 or cisplatin 75 mg/m², d1) every 3 weeks (Q3W) for a total of 4 cycles.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 gene and having received the first-line targeted therapy approved by the National Medical Products Administration (NMPA). 4. Failure of previous tyrosine kinase inhibitor (TKI) treatment and currently having no standard TKI treatment available. 5. Positive for PD-L1 (tumor proportion score, TPS ≥ 1%) confirmed by the central laboratory test or local test. 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. Female subjects of childbearing potential, and male subjects whose partners are females of childbearing age, need to adopt a highly effective contraceptive measure during the study treatment period and for at least 6 months after the last administration. 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. Treatment received as listed in the protocol, including immunologically mediated treatment; drugs targeting the anti-VEGF pathway, etc. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed objective response rate (ORR) | Up to approximately 25 months | Evaluate the investigator-assessed objective response rate (ORR) of JS207 combined with pemetrexed and platinum-based chemotherapy 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-assessed objective response rate (DCR) | Up to approximately 25 months | 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 Progression-Free Survival (PFS) | Up to approximately 25months | 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) | Up to approximately 25 months | The OS is defined as the time from the first administration of the drug to death due to any cause |
| Adverse Event | Up to approximately 25 months | Collect Serious Adverse Events (SAEs) and Adverse Events (AEs) from the time of signing the Informed Consent Form (ICF) until the safety follow-up visit.Evaluate the safety of the investigational drug |
| Number of participants with Laboratory examination indices | Up to approximately 25 months | Collect all laboratory examinations during the study period or the safety follow-up period. The investigator must review the laboratory examination results, record the review findings, and record any clinically significant changes that occur during the study period as Adverse Events. Evaluate the safety of the investigational drug |
| Investigator-assessed Duration of Response (DoR) | Up to approximately 25 months | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity(NAb) | Up to approximately 25 months | The immunogenicity of JS207, including the incidence rate of neutralizing antibodies (NAb) (if applicable) |
| Expression level of PD-L1 in tumor tissues | Up to approximately 5 months | The correlation between the expression level of PD-L1 in tumor tissues and the therapeutic effect |
| Immunogenicity(ADA) | Up to approximately 25 months | The immunogenicity of JS207, including the titer of ADA |
| the trough concentrations (PK) | Up to approximately 25 months | To characterize the trough concentrations of JS207 |
Countries
China
Contacts
Primary ContactYing Zhang, Master
Backup ContactHuiyu Lan, Master
Outcome results
None listed