Clinical Trial

PNOC007: H3.3K27M Specific Peptide Vaccine Combined with poly-ICLC for the Treatment of newly diagnosed HLA-A2+ H3.3K27M Positive Diffuse Intrinsic Pontine Glioma (DIPG) as well as other newly diagnosed HLA-A2+ H3.3K27M Positive Gliomas

PNOC007 (Stratum A & B) Study Publication

PNOC007 is now closed, and clinical trial results are now available as published in the Neuro-Oncology in December 2020.

viewable here:

Immunotherapy, particularly active vaccinations, has the potential to develop as an effective and safe modality for patients with pediatric malignant gliomas. Vaccines using specific peptides, in comparison to whole glioma-derived antigens, may induce glioma-specific immune responses without theoretical concerns of auto-immune encephalitis. Use of modified peptides (peptides in which amino acid residues are replaced from the wild-type sequence) may allow us to induce more efficient T-cell responses than natural antigens in whole glioma cells. Recent published laboratory data have also shown that administration of poly-ICLC along with the synthetic peptides remarkably enhances the induction of anti-peptide cytotoxic T lymphocyte (CTL) responses and trafficking of antigen-specific T-cells to the brain tumor sites.  PD-1 plays an important role in suppressing the immune system by inhibiting T cell inflammatory activity and has been shown to play a role in tumor evasion of the immune system. We hypothesize that the combination of PD-1 inhibition with the H3.3K27M specific peptide vaccine will improve activity of the peptide vaccine, by amplifying the response of peptide-primed T cells against the tumor.

Stratum A:

• To assess the safety of repeated administration of the H3.3K27M epitope specific vaccine in HLA-A2 (02:01)+ children with H3.3K27M positive DIPGs.

• To determine the overall survival at 12 months (OS12) in HLA-A2 (02:01)+ children with DIPG that are treated with repeated administration of the H3.3K27M peptide.

Stratum B:

• To assess the safety of repeated administration of the H3.3K27M epitope specific vaccine in HLA-A2 (02:01)+ children with H3.3K27M positive midline gliomas other than DIPG, including spinal cord gliomas.

Stratum C:

• To assess the safety of repeated administration of the H3.3K27M epitope specific vaccine in combination with the PD-1 inhibitor nivolumab in HLA-A2 (02:01)+ children with H3.3K27M positive midline gliomas including DIPG and midline gliomas (excluding spinal cord tumors).

Funding is provided by The V Foundation and BMS.

PNOC007 (Stratum A & B) Study Publication

PNOC007 is now closed, and clinical trial results are now available as published in the Neuro-Oncology in December 2020.

viewable here:

Immunotherapy, particularly active vaccinations, has the potential to develop as an effective and safe modality for patients with pediatric malignant gliomas. Vaccines using specific peptides, in comparison to whole glioma-derived antigens, may induce glioma-specific immune responses without theoretical concerns of auto-immune encephalitis. Use of modified peptides (peptides in which amino acid residues are replaced from the wild-type sequence) may allow us to induce more efficient T-cell responses than natural antigens in whole glioma cells. Recent published laboratory data have also shown that administration of poly-ICLC along with the synthetic peptides remarkably enhances the induction of anti-peptide cytotoxic T lymphocyte (CTL) responses and trafficking of antigen-specific T-cells to the brain tumor sites.  PD-1 plays an important role in suppressing the immune system by inhibiting T cell inflammatory activity and has been shown to play a role in tumor evasion of the immune system. We hypothesize that the combination of PD-1 inhibition with the H3.3K27M specific peptide vaccine will improve activity of the peptide vaccine, by amplifying the response of peptide-primed T cells against the tumor.

Stratum A:

• To assess the safety of repeated administration of the H3.3K27M epitope specific vaccine in HLA-A2 (02:01)+ children with H3.3K27M positive DIPGs.

• To determine the overall survival at 12 months (OS12) in HLA-A2 (02:01)+ children with DIPG that are treated with repeated administration of the H3.3K27M peptide.

Stratum B:

• To assess the safety of repeated administration of the H3.3K27M epitope specific vaccine in HLA-A2 (02:01)+ children with H3.3K27M positive midline gliomas other than DIPG, including spinal cord gliomas.

Stratum C:

• To assess the safety of repeated administration of the H3.3K27M epitope specific vaccine in combination with the PD-1 inhibitor nivolumab in HLA-A2 (02:01)+ children with H3.3K27M positive midline gliomas including DIPG and midline gliomas (excluding spinal cord tumors).

Funding is provided by The V Foundation and BMS.

How to Enroll

If you believe your child or patient is eligible for this trial, contact the closest participating site or email us for more information.