Ignite Creation Date:
2024-05-06 @ 7:31 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06048315
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-09-21
First Post:
2023-09-10
Brief Title:
A Single Center Single Arm Clinical Study on the Treatment of Advanced Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations and Failed EGFR TKIs With the Combination of Enrotinib and Paclitaxel Monoclonal Antibody
Sponsor:
Degan Lu
Organization:
Qianfoshan Hospital
Study Overview
Official Title:
A Single Center Single Arm Clinical Study on the Treatment of Advanced Non-small Cell
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Lung cancer is the second most common malignancy and mortality rate in the world In the United States and Europe approximately 10 to 15 of NSCLC patients have epidermal growth factor receptor EGFR-sensitive mutations with higher mutation rates of 30 to 40 in Asia and objective response rates ORRs of 76 to 80 with EGFR Tyrosine Kinase Inhibitor TKI-targeted therapy However resistance mechanisms such as EGFR MET PIK3CA and BRAF gene alterations occur with the development of resistance to EGFR-TKI therapy Median Progression Free Survival mPFS for only 28-32 months The median overall survival mOS is only 75-106 months Due to the variety of mechanisms of resistance to EGFR-TKIs and the limited efficacy of chemotherapy it is necessary to provide salvage treatment for advanced non-small cell lung cancer that is positive for EGFR-sensitive mutations and has failed EGFR TKIs
Anlotinib is a novel multi-target tyrosine kinase inhibitor TKI used to inhibit tumor angiogenesis and proliferative signaling The main targets of anlotinib include tyrosine kinase vascular endothelial growth factor receptor 1-3 VEGFr1-3 fibroblast growth factor receptor 1-4 Fibroblast Growth Factor Receptor 1-4 platelet-β derived growth factor receptor α and β and stem cell factor receptor Anlotinib is rapidly absorbed through the intestine has high bioavailability a half-life of 5 days and is convenient for oral administration which is conducive to improving patient dependence IN MAY 2018 THE CHINA FOOD AND DRUG ADMINISTRATION APPROVED ANLOTINIB FOR MARKETING ENTERED THE MEDICAL INSURANCE CATALOG IN OCTOBER OF THE SAME YEAR AND WAS RECOMMENDED BY THE CHINESE SOCIETY OF CLINICAL ONCOLOGY CSCO FOR THE THIRD-LINE TREATMENT OF LUNG CANCER IN 2019
Penpulimab is a humanized immunoglobulin G1 monoclonal antibody IgG1 which is a class 1 new drug jointly developed by Zhongshan Akeso Biopharmaceutical Co Ltd and Chia Tai Tianqing Pharmaceutical Group Co Ltd which can specifically bind to PD-1 molecules on the surface of T lymphocytes thereby blocking the PD-1PD-L1 pathway that leads to tumor immune tolerance and reactivating the anti-tumor activity of T lymphocytes to achieve the purpose of treating tumors A number of preclinical in vitro trials have verified the effect of PEAMPLIMAB in blocking PD-1 pathway and the results of preclinical pharmacodynamics animal pharmacokinetics and toxicology have shown that PEAMPLIMAB has good stability reduced host cell protein residues and can effectively bind to antigens and eliminate Fc-mediated effector function with higher safety
AK105-201 is a multicenter double-blind randomized controlled phase III clinical trial evaluating the efficacy and safety of pianpulimab combined with carboplatin paclitaxel in the first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer the primary endpoint of the study was PFS and the secondary endpoint was OS and the results showed that the mPFS group of pianpulimab and the control group were 76m and 42m respectively and the HR was 044 reducing the risk of disease progression by 56 In the 2022 CSCO guidelines for the diagnosis and treatment of non-small cell lung cancer peamplimab combined with platinum-containing chemotherapy is recommended as the first-line treatment for stage IV driver-free squamous cell carcinoma Grade II In advanced patients with EGFR TKIs resistance pemetrexed chemotherapy has a good efficacy with a median PFS of 283 months and a response rate of 22 The AK105-203 study is a multicenter phase II clinical study led by Professors Jiao Shun and Bai Li of the Chinese PLA General Hospital of the Peoples Liberation Army of Anlotinib combined with péamplimab in the first-line treatment of hepatocellular carcinoma with a median follow-up of 23 months and mPFS of 88 months
Therefore based on the results of the current study on immunosuppressants and antiangiogenic drugs for the treatment of NSCLC and the current research status in patients with advanced NSCLC who are positive for EGFR-sensitive mutations and have failed EGFR TKIs we expect to conduct an exploratory clinical study of PD-1 antibody péamplimab combined with anlotinib in patients with advanced NSCLC who are positive for EGFR-sensitive mutations and have failed EGFR TKIs with the aim of evaluating the safety of this combination It was further investigated whether this combination could further improve the survival benefit of patients with advanced NSCLC
Anlotinib is a novel multi-target tyrosine kinase inhibitor TKI used to inhibit tumor angiogenesis and proliferative signaling The main targets of anlotinib include tyrosine kinase vascular endothelial growth factor receptor 1-3 VEGFr1-3 fibroblast growth factor receptor 1-4 Fibroblast Growth Factor Receptor 1-4 platelet-β derived growth factor receptor α and β and stem cell factor receptor Anlotinib is rapidly absorbed through the intestine has high bioavailability a half-life of 5 days and is convenient for oral administration which is conducive to improving patient dependence IN MAY 2018 THE CHINA FOOD AND DRUG ADMINISTRATION APPROVED ANLOTINIB FOR MARKETING ENTERED THE MEDICAL INSURANCE CATALOG IN OCTOBER OF THE SAME YEAR AND WAS RECOMMENDED BY THE CHINESE SOCIETY OF CLINICAL ONCOLOGY CSCO FOR THE THIRD-LINE TREATMENT OF LUNG CANCER IN 2019
Penpulimab is a humanized immunoglobulin G1 monoclonal antibody IgG1 which is a class 1 new drug jointly developed by Zhongshan Akeso Biopharmaceutical Co Ltd and Chia Tai Tianqing Pharmaceutical Group Co Ltd which can specifically bind to PD-1 molecules on the surface of T lymphocytes thereby blocking the PD-1PD-L1 pathway that leads to tumor immune tolerance and reactivating the anti-tumor activity of T lymphocytes to achieve the purpose of treating tumors A number of preclinical in vitro trials have verified the effect of PEAMPLIMAB in blocking PD-1 pathway and the results of preclinical pharmacodynamics animal pharmacokinetics and toxicology have shown that PEAMPLIMAB has good stability reduced host cell protein residues and can effectively bind to antigens and eliminate Fc-mediated effector function with higher safety
AK105-201 is a multicenter double-blind randomized controlled phase III clinical trial evaluating the efficacy and safety of pianpulimab combined with carboplatin paclitaxel in the first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer the primary endpoint of the study was PFS and the secondary endpoint was OS and the results showed that the mPFS group of pianpulimab and the control group were 76m and 42m respectively and the HR was 044 reducing the risk of disease progression by 56 In the 2022 CSCO guidelines for the diagnosis and treatment of non-small cell lung cancer peamplimab combined with platinum-containing chemotherapy is recommended as the first-line treatment for stage IV driver-free squamous cell carcinoma Grade II In advanced patients with EGFR TKIs resistance pemetrexed chemotherapy has a good efficacy with a median PFS of 283 months and a response rate of 22 The AK105-203 study is a multicenter phase II clinical study led by Professors Jiao Shun and Bai Li of the Chinese PLA General Hospital of the Peoples Liberation Army of Anlotinib combined with péamplimab in the first-line treatment of hepatocellular carcinoma with a median follow-up of 23 months and mPFS of 88 months
Therefore based on the results of the current study on immunosuppressants and antiangiogenic drugs for the treatment of NSCLC and the current research status in patients with advanced NSCLC who are positive for EGFR-sensitive mutations and have failed EGFR TKIs we expect to conduct an exploratory clinical study of PD-1 antibody péamplimab combined with anlotinib in patients with advanced NSCLC who are positive for EGFR-sensitive mutations and have failed EGFR TKIs with the aim of evaluating the safety of this combination It was further investigated whether this combination could further improve the survival benefit of patients with advanced NSCLC
Detailed Description:
Non-small cell lung cancer is the most common type of lung cancer accounting for 80-85 of all lung cancers and about 57 of patients with advanced NSCLC have distant metastases at the time of diagnosis although chemotherapy targeted therapy and anti-angiogenic drugs have become the cornerstone of the treatment of advanced NSCLC but the emergence of immune checkpoint inhibitors in recent years has changed the treatment model of NSCLC Immune checkpoint inhibitors enhance the bodys antitumor activity by inhibiting the immune escape mechanism of tumors and prolong the survival time of NSCLC patients According to statistics the 5-year survival rate of NSCLC patients who join immunotherapy and undergo multi-line therapy can reach 16
Previous studies have confirmed that anti-angiogenic drugs and immunotherapy have the effect of improving tumor microenvironment basic translational and clinical studies have shown that immune checkpoint inhibitors and anti-angiogenic drugs have a synergistic effect anti-angiogenic drugs can exert immunosuppressive effects by preventing immune invasion of tumors through tissue remodeling and fibrosis and patients can benefit from PD-1PD-L1 inhibitors combined with anti-angiogenic therapy
In the CheckMate 057 and KEYNOTE-001 studies the ORRs of patients with advanced NSCLC treated with anti-PD-1 monotherapy were 19 mPFS 23 months and 194 mFS 37 months respectively The results of Wangpl et al demonstrated that anti-PD-1 combined with anlotinib in the treatment of advanced NSCLC had an ORR of 284 a DCR of 866 and an mPFS of 69 months 95 CI 55-83 months confirming that the combination therapy of anlotinib and anti-PD-1 drugs has a good efficacy and can be used as a second- or third-line treatment in previously treated patients with advanced NSCLC indicating VEGF-VEGFR2 and PD-1- The dual inhibition of the PD-L1 pathway has clinical applicability
Previous studies have confirmed that anti-angiogenic drugs and immunotherapy have the effect of improving tumor microenvironment basic translational and clinical studies have shown that immune checkpoint inhibitors and anti-angiogenic drugs have a synergistic effect anti-angiogenic drugs can exert immunosuppressive effects by preventing immune invasion of tumors through tissue remodeling and fibrosis and patients can benefit from PD-1PD-L1 inhibitors combined with anti-angiogenic therapy
In the CheckMate 057 and KEYNOTE-001 studies the ORRs of patients with advanced NSCLC treated with anti-PD-1 monotherapy were 19 mPFS 23 months and 194 mFS 37 months respectively The results of Wangpl et al demonstrated that anti-PD-1 combined with anlotinib in the treatment of advanced NSCLC had an ORR of 284 a DCR of 866 and an mPFS of 69 months 95 CI 55-83 months confirming that the combination therapy of anlotinib and anti-PD-1 drugs has a good efficacy and can be used as a second- or third-line treatment in previously treated patients with advanced NSCLC indicating VEGF-VEGFR2 and PD-1- The dual inhibition of the PD-L1 pathway has clinical applicability
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None