Abstract CT057: Evaluation of tumor associated P30-peptide antigen (ETAPA): Safety and immunogenicity in a phase 1b trial in glioblastoma

We developed a novel peptide-based vaccine, P30-EPS, which combines the universal class II-binding P30 epitope derived from tetanus toxoid with HLA-A2:01 class I peptides from tumor-associated antigens (TAAs) EphA2, CMV pp65, and survivin. Administered with poly-ICLC as an adjuvant, this vaccine induces inflammatory cytokines such as IFN-γ, TNF-α, and IL-6 to enhance antigen presentation and CD8+ T-cell activation, while the tetanus toxoid-derived P30 peptide serves as a helper epitope to amplify CD4+ T-cell responses and boost overall immunogenicity. This vaccine is specifically designed to enhance CD4 T cell engagement and boost immune responses against antigens commonly expressed by glioblastoma cells. The phase 1b ETAPA trial (NCT05283109) is enrolling both CMV- and CMV+ patients with newly diagnosed, unmethylated GBM to evaluate the safety and immunogenicity of P30-EPS. Patients receive seven doses of the vaccine following standard radiation therapy and concomitant temozolomide treatment, with an escalating peptide dose. A “3+3” dose-escalation strategy with 300 μg and 400 µg per peptide was used to assess dose-limiting toxicities (DLT) following vaccination with P30-EPS. Patients were observed for DLT from vaccine 1 until 30 days after vaccine 5. Primary outcomes include safety, while secondary objectives focus on peripheral blood immune responses, specifically TAA-specific T cell activity assessed by IFNγ ELISPOT and polyfunctional flow cytometry, alongside survival metrics. P30-EPS vaccination at both dose levels (n=12) was well-tolerated in CMV+ and CMV- patients with no serious adverse events (SAEs) or DLTs, all reported adverse events were mild (grade 1-2). Enrollment continues at the 400 μg dose. Four of the initial six patients had increased vaccine specific immune activation by ELISPOT at vaccine 5 compared to baseline. Interestingly, increased IFN-γ response was not dependent on patient HLA A2:01 type. Furthermore, patients which developed vaccine specific immunity had higher baseline B cell percentages. Comprehensive data from flow cytometry and scRNA VDJ TCR sequencing of B and T cell receptors in PBMCs, collected both pre- and post-vaccination will be presented, this data will inform subsequent steps in clinical development.

Duke Scholars

Author David Michael Ashley Neurosurgery

Author Mustafa Khasraw Neurosurgery

Author Margaret Johnson Neurosurgery

Author Henry Seth Friedman Neurosurgery, Neuro-Oncology