Advanced non-squamous non-small cell lung cancer positive for driver gene and treatment failure with TKI therapy
Conditions
Interventions
Experimental group:JS207 in combination with Pemetrexed, Carboplatin or Cisplatin for the first 4 cycles
JS207 in combination with Pemetrexed from the 5th cycle
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age 18 to 75 years (inclusive) at the time of signing informed consent, both male and female; 2. Histologically or cytologically confirmed local late (stage IIIB/IIIC) or metastatic or recurrent non-squamous NSCLC that is not eligible for radical surgery or radical radiotherapy; 3. Driver gene positive and NMPA-approved first-line targeted therapy, including but not limited to one of the following: EGFR-sensitive mutations (exon 18 G719X mutation, exon 19 deletion mutation, exon 20 S768I or T790M mutation, exon 21 L858R or L861Q mutation), ALK fusion, ROS1 fusion, BRAFV600E mutation, NTRK fusion, MET14 exon skipping mutation, RET fusion; 4. Failure of prior TKI therapy and no current standard TKI therapy. For patients with different mutations, the specific requirements are as follows: For patients with EGFR-sensitive mutations, one of the following conditions must be met: 1) No T790M mutation after failure of previous first- or second-generation EGFR-TKI monotherapy; 2) subjects who have failed three prior generations of EGFR-TKI monotherapy (regardless of their EGFR T790M mutation status); 3) For subjects with recurrent non-squamous NSCLC who have received prior neoadjuvant/consolidation/adjuvant therapy (chemotherapy, radiotherapy, or other treatments): a) Subjects who have progressed on the last treatment (surgery, chemotherapy and adjuvant EGFR-TKI therapy, whichever is later) to the time interval of recurrence of more than 6 months before receiving the third generation of EGFR-TKI monotherapy (direct therapy or follow-up therapy with T790M mutation positivity after failure of the first and second generation EGFR-TKI) can be enrolled; b) Subjects who have progressed on adjuvant first-generation EGFR-TKI postoperatively, and who have progressed on adjuvant therapy or within 6 months after discontinuation of the established length of treatment with positive T790M mutation, and who have progressed on monotherapy with a third-generation EGFR-TKI may be enrolled (if adjuvant chemotherapy has been received postoperatively, the time interval between the last adjuvant chemotherapy and the time interval of recurrence after adjuvant EGFR-TKI therapy should also be more than 6 months); c) Subjects who have progressed during single-agent adjuvant/consolidation therapy with a third-generation EGFR-TKI or within 28 days after discontinuation of the established length of treatment may be enrolled (if adjuvant chemotherapy is received postoperatively, the interval between the last adjuvant and relapse should also be more than 6 months); For ALK fusion-positive patients, one of the following criteria is required: 1) Failure to receive a third-generation ALK-TKI after treatment failure with a previous first- or second-generation ALK-TKI; 2) failure of previous three generations of ALK-TKI therapy; 3) For subjects with recurrent non-squamous NSCLC who have received neoadjuvant/consolidation/adjuvant therapy (chemotherapy, radiotherapy or other treatments) in the past, subjects who have progressed during the treatment of the third generation of ALK-TKI monotherapy adjuvant therapy or within 28 days after the completion of the established length of treatment and the interval between the last treatment and recurrence of other systemic antitumor therapies is more than 6 months can be enrolled; For patients with other mutations, failure of prior TKI therapy is required; Note: The above TKIs only include products that have been approved for marketing by
Exclusion criteria
Exclusion criteria: 1. Concomitant study disease states of: a. Histological or cytological pathology of the tumor confirmed with neuroendocrine tumor (including small cell lung cancer, large cell neuroendocrine carcinoma, etc.), or more than 10% of squamous cell carcinoma components; b. Patients with known meningeal metastases; c. Patients with symptomatic brain metastases; For asymptomatic patients with brain metastases, those who are assessed as stable by the investigator can be enrolled, including: 1) those who have received radiation therapy for brain metastases and remain stable, the criteria for stability need to meet all of the following conditions: symptomatic treatment such as corticosteroids and mannitol needs to be discontinued at least 7 days before study drug administration, and no disease progression is found after the end of treatment for brain metastases and before the first use of study drug imaging compared with pre-treatment imaging (at least 4 weeks apart); 2) Patients with asymptomatic brain metastases who have not received local treatment need to meet all the following conditions: no use of corticosteroids and mannitol to control symptoms related to brain metastases, no long-diameter >=1cm of any brain metastases, no metastases of the midbrain, pons, bulbar or spinal cord, and no history of intracranial hemorrhage in the past; d. The tumor surrounds important blood vessels or has obvious necrosis or cavitation, and in the opinion of the investigator, it may cause a risk of bleeding; Clinically significant hemoptysis (>=2.5 ml) or tumor hemorrhage of any cause within one month prior to the first dose of study drug; f. Pleural effusion, pericardial effusion, or ascites that are uncontrollable or require repeated drainage (once a month or more); Subjects whose symptoms are stable for at least 1 week after drainage may be enrolled; g. Spinal cord compression without surgery and/or radiotherapy, or previously diagnosed spinal cord compression with no clinical evidence of stable disease prior to enrollment >=4 weeks; 2. Have received any of the following treatments: a. Immune-mediated therapy, including but not limited to anti-PD-1, anti-PD-L1 therapy; b. platinum-doublet chemotherapy; Only patients who received adjuvant or neoadjuvant platinum-doublet chemotherapy with a time interval of >6 months from the last chemotherapy to relapse may be enrolled; c. Anti-VEGF pathway target agents; d. Receipt of any investigational drug within 4 weeks or 5 half-lives prior to the first dose of study drug, whichever is shorter; e. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, or the subject is in the follow-up period of the interventional clinical study; f. Requires systemic therapy with corticosteroids (> 10 mg prednisone equivalent dose per day) or other immunosuppressants within 2 weeks prior to the first dose of study drug. Inhaled or topical corticosteroids are permitted. Receipt of short-term corticosteroids (as before intravenous contrast) within 2 weeks prior to the first dose is permitted; g. Receipt of proprietary Chinese medicine with anti-tumor indication within 1 week prior to the first dose; h. Subjects who have received immunomodulatory drugs (thymopeptide, interferon, interleukin, etc.) within 2 weeks or 5 half-lives prior to the first dose, or subjects who need to continue treatment with these drugs during the study, whichever is shorter; i. Those who have received a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Investigator-assessed objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Immunogenicity of JS207, including the incidence and titer of anti-drug antibody, and the incidence of Neutralising antibodies (if applicable).;Overall survival;Duration of response;Progression-free survival;Laboratory test Investigation;Efficacy relevance with PD-L1 expression level in neoplasm tissue;Adverse event;Disease control rate;JS207 blood concentration; | — |
Countries
China
Contacts
Public ContactZhou Qing
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed