Ignite Creation Date:
2025-12-24 @ 7:43 PM
Ignite Modification Date:
2025-12-29 @ 7:57 AM
Study NCT ID:
NCT03893903
Status:
COMPLETED
Last Update Posted:
2025-03-14
First Post:
2018-08-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
AMPLIFYing NEOepitope-specific VACcine Responses in Progressive Diffuse Glioma
Sponsor:
German Cancer Research Center
Organization:
Study Overview
Official Title:
AMPLIFYing NEOepitope-specific VACcine Responses in Progressive Diffuse Glioma - a Randomized, Open Label, 3 Arm Multicenter Phase I Trial to Assess Safety, Tolerability and Immunogenicity of IDH1R132H-specific Peptide Vaccine in Combination with Checkpoint Inhibitor Avelumab
Status:
COMPLETED
Status Verified Date:
2025-03
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:
AMPLIFY-NEOVAC
Brief Summary:
The trial will address safety and tolerability of the combination of the IDH1R132H-specific vaccine with checkpoint blockade and seeks to explore predictive biomarkers for response to checkpoint blockade in post-treatment tumor tissue. The study will enroll 48 evaluable patients (presumably, 60 in total) with IDH1R132H-mutated gliomas with an unfavorable molecular profile (no 1p/19q co-deletion, nuclear ATRX- loss) progressive after radiotherapy and alkylating chemotherapy eligible for re-resection. After diagnosis of recurrent disease on imaging patients will be randomized assigned in a 1:1:2 ratio into three arms. Arm 1 (12 patients) will receive three IDH1R132H peptide vaccines alone in two week intervals. Arm 2 (12 patients) will receive three IDH1R132H peptide vaccines in combination with three doses of Avelumab in two week intervals. Arm 3 (24 patients) will receive three doses of Avelumab in two week intervals. After 6 weeks of treatment patients (Arms 1-3) will undergo planned re-resection. Four weeks after the operation treatment will be resumed consisting of five additional vaccines (Arm 1+2) in 4 week intervals, followed by maintenance vaccines until progression in three months' intervals after a pause of 16 weeks. Avelumab will be administered in monthly intervals in Arms 2 and 3 starting four weeks after the operation until progression.
Key outcome parameters will be safety and immunogenicity (Arms 1 and 2) based on peripheral and intratumoral immune analyses assessed 9 months after re-resection.
Key outcome parameters will be safety and immunogenicity (Arms 1 and 2) based on peripheral and intratumoral immune analyses assessed 9 months after re-resection.
Detailed Description:
The standard of care (SOC) treatment of patients with malignant gliomas is - independent of molecular markers - still confined to surgery, irradiation and alkylating chemotherapy as targeted therapies to date have failed to prove superiority over standard of care in controlled trials. At the same time, novel concepts in immunotherapy have evolved with the identification of potential (neo)epitopes and phase III clinical trials investigating the efficacy of checkpoint inhibitors. Despite patients frequently undergoing resection of recurrent tumor, patient selection criteria for innovative immunotherapy in glioma have been hampered by the lack of availability of post-treatment tumor tissue. Neoepitope-specific vaccines have gained considerable interest also in a challenging disease such as glioma. IDH1R132H, a frequent driver mutation in gliomas, was previously identified to contain a neoepitope. A peptide vaccine targeting this epitope is currently tested in a phase I first-in-man multicenter clinical trial. The clinical phase of this trial was completed in Q3 2017 with 32 patients treated. The primary endpoints were met by demonstrating safety and immunogenicity. Checkpoint inhibitors are tested in unselected populations of glioma patients despite evidence that response is associated with high mutational load, which is infrequent in untreated gliomas, but may occur particularly after long periods of exposure to alkylating chemotherapy.
The trial will address safety and tolerability of the combination of the IDH1R132H-specific vaccine with checkpoint blockade and seeks to explore predictive biomarkers for response to checkpoint blockade in post-treatment tumor tissue. The study will enroll 48 evaluable patients (presumably, 60 in total) with IDH1R132H-mutated gliomas with an unfavorable molecular profile (no 1p/19q co-deletion, nuclear ATRX loss) progressive after radiotherapy and alkylating chemotherapy eligible for re-resection. After diagnosis of recurrent disease on imaging patients will be randomized assigned in a 1:1:2 ratio into three arms. Arm 1 (12 patients) will receive three IDH1R132H peptide vaccines alone in two week intervals. Arm 2 (12 patients) will receive three IDH1R132H peptide vaccines in combination with three doses of Avelumab, a humanized anti-PD-L1 antibody approved for patients with Merkel cell carcinoma and urothelial cancer, in two week intervals. Arm 3 (24 patients) will receive three doses of Avelumab in two week intervals. After 6 weeks of treatment patients (Arms 1-3) will undergo planned re-resection. A safety MRI will be performed three weeks after initiation of the experimental treatment. Four weeks after the operation treatment will be resumed consisting of five additional vaccines (Arm 1+2) in 4 week intervals, followed by maintenance vaccines until progression in three months' intervals after a pause of 16 weeks. Avelumab will be administered in monthly intervals in Arms 2 and 3 starting four weeks after the operation until progression.
Key outcome parameters will be safety and immunogenicity (Arms 1 and 2) based on peripheral and intratumoral immune analyses assessed 9 months after re-resection. Additional exploratory analyses will determine efficacy (all Arms), dependent on predictive molecular immune and imaging biomarkers, such as increased mutational load (Arm 3). Based on the experience in the NOA-04 and CATNON trials the expected time to second progression is 9-12 months.
The trial is supported by the German Cancer Consortium (DKTK) and the Neurooncology Working Group of the German Cancer Society (NOA).
The trial will address safety and tolerability of the combination of the IDH1R132H-specific vaccine with checkpoint blockade and seeks to explore predictive biomarkers for response to checkpoint blockade in post-treatment tumor tissue. The study will enroll 48 evaluable patients (presumably, 60 in total) with IDH1R132H-mutated gliomas with an unfavorable molecular profile (no 1p/19q co-deletion, nuclear ATRX loss) progressive after radiotherapy and alkylating chemotherapy eligible for re-resection. After diagnosis of recurrent disease on imaging patients will be randomized assigned in a 1:1:2 ratio into three arms. Arm 1 (12 patients) will receive three IDH1R132H peptide vaccines alone in two week intervals. Arm 2 (12 patients) will receive three IDH1R132H peptide vaccines in combination with three doses of Avelumab, a humanized anti-PD-L1 antibody approved for patients with Merkel cell carcinoma and urothelial cancer, in two week intervals. Arm 3 (24 patients) will receive three doses of Avelumab in two week intervals. After 6 weeks of treatment patients (Arms 1-3) will undergo planned re-resection. A safety MRI will be performed three weeks after initiation of the experimental treatment. Four weeks after the operation treatment will be resumed consisting of five additional vaccines (Arm 1+2) in 4 week intervals, followed by maintenance vaccines until progression in three months' intervals after a pause of 16 weeks. Avelumab will be administered in monthly intervals in Arms 2 and 3 starting four weeks after the operation until progression.
Key outcome parameters will be safety and immunogenicity (Arms 1 and 2) based on peripheral and intratumoral immune analyses assessed 9 months after re-resection. Additional exploratory analyses will determine efficacy (all Arms), dependent on predictive molecular immune and imaging biomarkers, such as increased mutational load (Arm 3). Based on the experience in the NOA-04 and CATNON trials the expected time to second progression is 9-12 months.
The trial is supported by the German Cancer Consortium (DKTK) and the Neurooncology Working Group of the German Cancer Society (NOA).
Study Oversight
Has Oversight DMC:
True
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?:
False
Is an FDA AA801 Violation?: