Ignite Creation Date:
2024-05-06 @ 7:06 PM
Last Modification Date:
2024-10-26 @ 3:00 PM
Study NCT ID:
NCT05898763
Status:
RECRUITING
Last Update Posted:
2023-09-13
First Post:
2023-04-24
Brief Title:
TEIPP Immunotherapy in Patients With NSCLC
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
T-cell Epitopes Associated With Impaired Peptide Processing TEIPP- Targeting Immunotherapy in Patients With Relapsed Advanced Non Small Cell Lung Cancer NSCLC
Status:
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:
TEIPP
Brief Summary:
In this multicenter open label non-randomized phase III dose escalation study with extension cohort HLA-A0201-positive patients with non small cell lung cancer NSCLC can be included The primary aim of this study is determine the safety tolerability and immune modulating effects of the therapeutic LRPAP1 synthetic long peptide LRPAP7-30V-SLP vaccine TEIPP24 at different doses Secondary objectives are to assess the specificity and immune modulatory effects of the vaccine to assess the antigen and immune status of the patients and to determine progression free survival PFS overall survival OS and the radiological tumor response up to one year after first vaccination
Detailed Description:
Immunogenic tumors can be controlled by tumor-reactive Tcells either directly or after checkpoint blockade In the end most tumors will develop mechanisms to escape immune control One of such a mechanism is formed by the functional impairment of the intracellular peptide transporter TAP1TAP2 by mutation of downregulated expression As a result the presentation of conventional T-cell epitopes in HLA class I is lost and hence tumor-reactive CD8 T-cells fail to recognize and kill tumor cells This type of immune escape can occur in up to 50 of primary tumors and is increased in the metastatic lesions of such tumors The presence of these TAP defects correlate with worse clinicopathological parameters and has been associated with loss of durable benefit to checkpoint inhibition The unmet need therefore is the development of a therapy that can reinforce effective tumor-immunity to cancers displaying TAP-defects for which conventional therapeutic cancer vaccines andor checkpoint blockade do not work TEIPP therapy may fill this position by reinstalling an effective antitumor response to TAP-defective tumors thereby increasing the overall survival of patients failing first line therapy
In this prospective single arm multicenter open-label phase I-II clinical study HLA-A0201-positive patients with NSCLC failing first line of treatment will be enrolled in 3 cohorts and one extension cohort of 6 patients at the highest safe and tolerable dose combined with a checkpoint inhibitor targeting PD-1PD-L1 CPI to include 24 patients in total The maximal total treatment duration is 9 weeks The first 6 patients will be enrolled in cohort 1 the next 6 patients in cohort 2 the next 6 patients in cohort 3 The decision to start enrollment at the next dose level will be made by assessing the safety after 3 out of 6 patients at the previous dose level have completed vaccine therapy
Patients will receive an off the shelf TEIPP24 vaccine mixed with Montanide ISA-51 adjuvant which will be administered every three weeks for a period of three rounds of vaccination Patient cohort 1 will be treated with TEIPP24 at a dose of 20ug of peptide patients in cohort 2 with TEIPP24 at a dose of 40ug of peptide and patients in cohort 3 with TEIPP24 at a dose of 100ug of peptide Patients in the extension cohort will receive the highest safest dose in combination with pembrolizumab a CPI Patients will receive three rounds of vaccination three weeks apart via one subcutaneous SC injection in a limb The SC route of administration of TEIPP24 vaccine is dictated by the use of Montanide ISA51 Subsequently patients will be followed up to 1 year after the first vaccination
In this prospective single arm multicenter open-label phase I-II clinical study HLA-A0201-positive patients with NSCLC failing first line of treatment will be enrolled in 3 cohorts and one extension cohort of 6 patients at the highest safe and tolerable dose combined with a checkpoint inhibitor targeting PD-1PD-L1 CPI to include 24 patients in total The maximal total treatment duration is 9 weeks The first 6 patients will be enrolled in cohort 1 the next 6 patients in cohort 2 the next 6 patients in cohort 3 The decision to start enrollment at the next dose level will be made by assessing the safety after 3 out of 6 patients at the previous dose level have completed vaccine therapy
Patients will receive an off the shelf TEIPP24 vaccine mixed with Montanide ISA-51 adjuvant which will be administered every three weeks for a period of three rounds of vaccination Patient cohort 1 will be treated with TEIPP24 at a dose of 20ug of peptide patients in cohort 2 with TEIPP24 at a dose of 40ug of peptide and patients in cohort 3 with TEIPP24 at a dose of 100ug of peptide Patients in the extension cohort will receive the highest safest dose in combination with pembrolizumab a CPI Patients will receive three rounds of vaccination three weeks apart via one subcutaneous SC injection in a limb The SC route of administration of TEIPP24 vaccine is dictated by the use of Montanide ISA51 Subsequently patients will be followed up to 1 year after the first vaccination
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