Phase I/II Trial of IMA950 Multi-peptide Vaccine Plus Poly-ICLC in Glioblastoma

RATIONALE : IMA 950 is multi tumour-associated peptides (TUMAPs) vaccine, these peptides have been identified on primary glioblastoma multiforme (GBM) cells. Poly-ICLC is a potent vaccine adjuvant with broad innate and adaptive immune enhancing effects. IMA 950 and Poly-ICLC will be administered to patients alongside standard primary therapy for glioblastoma. This includes the alkylating drug temozolomide (TMZ). Effective vaccine-induced immune responses associated with prolonged survival have been observed in glioblastoma patients during TMZ adjuvant therapy, suggesting a possible synergistic effect. A second component of glioblastoma standard treatment is external beam irradiation of the tumor site post-surgery. As a side effect, potentially beneficial tumor-infiltrating immune cells may also be killed by radiation. However, the combination of radiation with immunotherapy has been suggested to be favorable both in pre-clinical models.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

1. Histological documentation of glioblastoma. For experimental purposes only, 5 additional grade III astrocytoma may be included (these cases will not be included in the endpoints analysis).
2. Patients must have completed radiation therapy with concomitant temozolomide.
3. HLA-A2 positive.
4. Eastern Cooperative Oncology Group performance status of 0 or 1 (Appendix1).
5. Age \> 18 years, life expectancy of least 4 months.
6. Patient must be on stable or decreasing dose of steroids, with a maximal dose of Dexamethasone of 4mg/day.
7. Adequate bone marrow, liver and kidney function.
8. Hepatitis B serology negative (HBcAg-seronegative)
9. Written (signed and dated) informed consent. Capable of co-operating with standard therapy and IMA950 with Poly-ICLC vaccinations and follow-up.

Exclusion Criteria:

1. Any other vaccination given within 2 weeks before first IMA950 vaccination.
2. History of cardiac disease: congestive heart failure \> New York heart association class 2, active CAD, cardiac requiring anti-arrhythmic therapy or uncontrolled hypertension.
3. History of HIV infection or chronic hepatitis B or C or clinical active infections.
4. Patients with evidence of history bleeding diathesis.
5. Pregnant or potentially pregnant patients. Women of childbearing age must be tested for pregnancy (serum or urine HCG) before treatment and must not contemplate pregnancy during the study

• DERIVEDMigliorini D, Dutoit V, Allard M, Grandjean Hallez N, Marinari E, Widmer V, Philippin G, Corlazzoli F, Gustave R, Kreutzfeldt M, Blazek N, Wasem J, Hottinger A, Koka A, Momjian S, Lobrinus A, Merkler D, Vargas MI, Walker PR, Patrikidou A, Dietrich PY. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Neuro Oncol. 2019 Jul 11;21(7):923-933. doi: 10.1093/neuonc/noz040. PMID 30753611