Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02149225 | GAPVAC Phase I Trial in Newly Diagnosed Glioblastoma Patients | PHASE1 | COMPLETED | 16 | — | — | Oct 1, 2014 | Jun 1, 2018 | Aug 7, 2018 | 6 | Denmark, Germany +3 |
Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) and percentage of patients with AEs and SAEs (listed per grade and MedDRA (Medical Dictionary for Regulatory Activities ) preferred terms) will be reported.
To analyze whether vaccinations with APVAC drug products plus poly-ICLC and GM-CSF induce immune responses in the patients. Peripheral blood mononuclear cells will be analyzed for the presence and functionality of T cells recognizing the peptides vaccinated within the individualized APVACs. * Immunogenicity rate: Number of vaccine induced T-cell responses normalized to the number of peptides vaccinated. * Immune responder rate: Number of patients with at least one vaccine induced T-cell response * Multi-TUMAP responder rate: Number of patients with at least two vaccine induced T-cell response * Average number of immune responses per patient
| Arm | Type | Description |
|---|---|---|
| APVAC1 and 2 vaccine plus polyICLC and GMCSF concurrent to TMZ | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| APVAC1 vaccine plus Poly-ICLC and GM-CSF | DRUG | APVAC1 vaccines (i.d.) will be individually assembled for each patient and can be applied to the patient approx. 3 months after enrollment. APVAC1 drug products are composed of 5 to 10 peptides from the GAPVAC warehouse. The APVAC1 vaccine will be applied concurrent to maintenance TMZ cycles after completion of chemoradiation therapy (CRT). Beginning on day 15 of the first maintenance TMZ cycle, patients will receive 11 vaccinations with APVAC1 drug products during 22 weeks. 578 μg per peptide per vial are used. Poly ICLC (1.5 mg s.c.) will be used as immunomodulator with all vaccinations except the second applications of APVAC1 (Day 2) and APVAC2 vaccines (Day 2\*) to avoid dose accumulation on consecutive days. The 2. immunomodulator GM-CSF (75 μg) will be applied i.d. with the first six vaccinations with both vaccines, APVAC1 and APVAC2. A total of 12 GM-CSF doses will be applied. GM-CSF will be applied to the APVAC vaccination site 10-30 min before injection of the APVACs. |
| APVAC2 vaccine plus Poly-ICLC and GM-CSF | DRUG | APVAC2 vaccines (i.d.) will be ready for use ca. 6 months after enrollment, as these peptides have to be newly synthesized for each patient following identification of the mutanome and corresponding mutated peptides in the HLA ligandome. APVAC2 drug products are composed of 1 or 2 peptides de novo synthesized for an individual patient. Patients will be repeatedly vaccinated with APVAC2 drug products beginning on day 15 of the 4. maintenance TMZ cycle. Patients will receive 8 vaccinations within 10 weeks. 578 μg per peptide per vial are used. Poly-ICLC (1.5 mg s.c.) will be used as immunomodulator with all vaccinations except the second applications of APVAC1 (Day 2) and APVAC2 vaccines (Day 2\*) to avoid dose accumulation on consecutive days. GM-CSF (75 μg) will be applied i.d. with the first six vaccinations with both vaccines, APVAC1 and APVAC2. A total of 12 GM-CSF doses will be applied. GM-CSF will be applied to the APVAC vaccination site 10-30 min before injection of the APVACs. |
Inclusion Criteria: 1. Histologically confirmed, newly diagnosed GB (astrocytoma WHO grade IV) 2. HLA phenotype defined by warehouse composition (HLA-A\*02:01 or HLA-A\*24:02 positive patients only; both as determined by a PCR-based 4-digit typing method) 3. Gross total resection (as defined by les...