Ignite Creation Date:
2024-05-06 @ 4:34 PM
Last Modification Date:
2024-10-26 @ 2:12 PM
Study NCT ID:
NCT05027100
Status:
UNKNOWN
Last Update Posted:
2022-07-01
First Post:
2021-08-22
Brief Title:
Tislelizumab Combined With Anlotinib and 2-cycles Irinotecan as Second Line Treatment of SCLC
Sponsor:
Haibo Zhang
Organization:
Guangzhou University of Traditional Chinese Medicine
Study Overview
Official Title:
One Arm Exploratory Study of Tislelizumab Combined With Anlotinib and 2-cycle Irinotecan Monotherapy as Second Treatment of Small Cell Lung Cancer
Status:
UNKNOWN
Status Verified Date:
2022-06
Last Known Status:
RECRUITING
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:
SCLC has short doubling time high proliferation rate and early widespread metastasis Most patients with SCLC have hematogenous metastasis SCLC is highly sensitive to initial chemoradiotherapy but the recurrence rate is high The strategy for local limited SCLC patients was chemotherapy plus chest radiotherapy In patients with extensive stage SCLC first-line platinum-based chemotherapy has been established as the standard treatment for patients with small cell lung cancer SCLC with better results Although the initial response to chemotherapy is high it is easy to relapse and develop drug resistance
In second-line therapy the single-agent activity of multiple chemotherapy agents has been demonstrated but a higher incidence of grade 3-4 hematological adverse events In the Passion study published by Wang Jie et al 10 the efficacy and safety of the antiangiogenic drug apatinib combined with carrizumab in the second-line treatment of small cell lung cancer were investigated A total of 59 patients were enrolled in the study Of the 47 patients in the extended phase the confirmed ORR was 340 95CI 209-493 with a median PFS of 36 months and a median OS of 84 months In patients with platinum sensitivity and platinum resistance ORR was 375 vs 323 MPFS was 36m vs 27m and MOS was 96m vs 80m Grade 3 treatment-related adverse events TRAEs occurred in 43 of the 59 patients 729 and 5 patients 85 were discontinued due to TRAEs The combination regimen showed potential antitumor activity in both platinum-sensitive and platinum-resistant cases
The research and exploration of small cell lung cancer can learn from the research idea in the field of non-small cell lung cancer The Checkmate9LA study reported in 2020ASCO 11 investigated the safety and efficacy of Nivolumab2 cycle chemotherapy in first-line treatment of non-small cell lung cancer with negative driver gene The MOS in the immunization combination group was significantly better than that in the chemotherapy group 156 months vs 109 months HR 066 and the 1-year survival rate was 63 vs 47 respectively The ORR in the immunization combination group was also improved 38 vs 25 and the MDOR was 113m vs 56m which was tolerable in terms of safety The incidence of grade 3-4 treatment-associated AE was 47 in the immune-combined group and 38 in the chemotherapy group From the perspective of mechanism chemotherapy can enhance the immunogenicity of tumor cells damage the immune cell inhibitory activity which can induce tumor cell apoptosis expression of MHC class 1 molecules increases and mature dendritic cells to promote the immune response in the design add 2 cycles of chemotherapy short-term intensive treatment make up the immune short board For example the early onset of slow and immune characteristic events such as large tumor load pseudo progression hyperrogression and other problems to achieve the optimization and upgrading of the scheme
Based on Rationale 307 Tislelizumab was approved on January 12 2021 for first-line treatment in combination with paclitaxel and carboplatin in patients with locally advanced or metastatic squamous non-small cell lung cancer t the same time Tislelizumab initial efficacy in patients with extensive small-cell lung cancrRational-206 study is a phase Ⅱ multi-cohort study of Tislelizumab combined with first-line platinum-containing chemotherapy in patients with advanced lung cancer in China The MPFS in the SCLC cohort was about 7 months and the MOS reached 156 months
Based on the above studies and data in the second-line treatment of SCLC anti-vascular targeted drugs combined with chemotherapy can obtain a certain survival benefit especially for patients with sensitive recurrence and the benefit is more significant he immune checkpoint inhibitors have gradually emerged in the second-line and later treatment of SCLC but the single drug effect has not been a great breakthrough a small molecule antiangiogenic targeted drug in China Anlotinib has obtained third-line and later indications of SCLC through ALTER1202 data and has been included in the 2019 CSCO Guidelines for the Diagnosis and Treatment of Primary Lung Cancer t the same time it is similar to the Checkmate9LA study regimen combined with two cycles of chemotherapy to improve the short-term efficacy Therefore Anlotinib combined with Tislelizumab a PD-1 inhibitor and 2 cycles of Irinotecan monotherapy were tried in second-line SCLC with the hope of breaking through the difficulties of high recurrence rate and rapid disease progression of existing second-line SCLC chemotherapy regardless of platinum-sensitive recurrence or platinum-resistant recurrence and providing more options for SCLC patients
In second-line therapy the single-agent activity of multiple chemotherapy agents has been demonstrated but a higher incidence of grade 3-4 hematological adverse events In the Passion study published by Wang Jie et al 10 the efficacy and safety of the antiangiogenic drug apatinib combined with carrizumab in the second-line treatment of small cell lung cancer were investigated A total of 59 patients were enrolled in the study Of the 47 patients in the extended phase the confirmed ORR was 340 95CI 209-493 with a median PFS of 36 months and a median OS of 84 months In patients with platinum sensitivity and platinum resistance ORR was 375 vs 323 MPFS was 36m vs 27m and MOS was 96m vs 80m Grade 3 treatment-related adverse events TRAEs occurred in 43 of the 59 patients 729 and 5 patients 85 were discontinued due to TRAEs The combination regimen showed potential antitumor activity in both platinum-sensitive and platinum-resistant cases
The research and exploration of small cell lung cancer can learn from the research idea in the field of non-small cell lung cancer The Checkmate9LA study reported in 2020ASCO 11 investigated the safety and efficacy of Nivolumab2 cycle chemotherapy in first-line treatment of non-small cell lung cancer with negative driver gene The MOS in the immunization combination group was significantly better than that in the chemotherapy group 156 months vs 109 months HR 066 and the 1-year survival rate was 63 vs 47 respectively The ORR in the immunization combination group was also improved 38 vs 25 and the MDOR was 113m vs 56m which was tolerable in terms of safety The incidence of grade 3-4 treatment-associated AE was 47 in the immune-combined group and 38 in the chemotherapy group From the perspective of mechanism chemotherapy can enhance the immunogenicity of tumor cells damage the immune cell inhibitory activity which can induce tumor cell apoptosis expression of MHC class 1 molecules increases and mature dendritic cells to promote the immune response in the design add 2 cycles of chemotherapy short-term intensive treatment make up the immune short board For example the early onset of slow and immune characteristic events such as large tumor load pseudo progression hyperrogression and other problems to achieve the optimization and upgrading of the scheme
Based on Rationale 307 Tislelizumab was approved on January 12 2021 for first-line treatment in combination with paclitaxel and carboplatin in patients with locally advanced or metastatic squamous non-small cell lung cancer t the same time Tislelizumab initial efficacy in patients with extensive small-cell lung cancrRational-206 study is a phase Ⅱ multi-cohort study of Tislelizumab combined with first-line platinum-containing chemotherapy in patients with advanced lung cancer in China The MPFS in the SCLC cohort was about 7 months and the MOS reached 156 months
Based on the above studies and data in the second-line treatment of SCLC anti-vascular targeted drugs combined with chemotherapy can obtain a certain survival benefit especially for patients with sensitive recurrence and the benefit is more significant he immune checkpoint inhibitors have gradually emerged in the second-line and later treatment of SCLC but the single drug effect has not been a great breakthrough a small molecule antiangiogenic targeted drug in China Anlotinib has obtained third-line and later indications of SCLC through ALTER1202 data and has been included in the 2019 CSCO Guidelines for the Diagnosis and Treatment of Primary Lung Cancer t the same time it is similar to the Checkmate9LA study regimen combined with two cycles of chemotherapy to improve the short-term efficacy Therefore Anlotinib combined with Tislelizumab a PD-1 inhibitor and 2 cycles of Irinotecan monotherapy were tried in second-line SCLC with the hope of breaking through the difficulties of high recurrence rate and rapid disease progression of existing second-line SCLC chemotherapy regardless of platinum-sensitive recurrence or platinum-resistant recurrence and providing more options for SCLC patients
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None