🧪 NOA-16 Trial

The NOA-16 Trial is a pioneering first-in-human clinical study investigating the safety, feasibility, and immunogenicity of a personalized mRNA-based neoantigen vaccine in patients with newly diagnosed glioblastoma.

• Full title: “A Personalized Multipeptide mRNA Vaccine in Patients with Newly Diagnosed MGMT-Unmethylated Glioblastoma”
• Sponsor: NOA (Neuro-Oncology Working Group of the German Cancer Society)
• Trial Phase: Phase I
• Study type: Open-label, multicenter, prospective
• Published: *Nature*, 2021

¹⁾

To assess whether personalized mRNA vaccines, designed to target individual tumor-specific neoantigens, can elicit robust anti-tumor immune responses in glioblastoma patients, with an acceptable safety profile.

• Adult patients with newly diagnosed glioblastoma
• Must have MGMT promoter-unmethylated tumors (poor response to temozolomide)
• HLA-A*02:01 positivity required for neoantigen prediction in some arms

• Individualized mRNA vaccines encoding up to 20 neoepitopes identified through:
  1. Whole-exome sequencing
  2. RNA-seq of the patient’s tumor
• Administered intradermally with poly-ICLC (an immune adjuvant)
• Given after surgery and radiotherapy

• Feasibility: Tumor sequencing, neoantigen prediction, and vaccine synthesis completed within 6–8 weeks
• Safety: No grade 3 or 4 treatment-related adverse events
• Immunogenicity:
  1. 93% of patients mounted T cell responses to at least one neoantigen
  2. Responses were detected in both CD4⁺ and CD8⁺ compartments
  3. T cell responses were polyfunctional and durable

• Demonstrated the clinical feasibility of truly personalized mRNA cancer vaccines
• Provided a foundation for further trials in glioma and other solid tumors
• Highlighted potential of mRNA platforms beyond infectious diseases

• Small sample size (n = 8 evaluable patients)
• Limited efficacy data due to early-phase design
• No control group
• Restricted to MGMT-unmethylated glioblastomas and certain HLA types

The NOA-16 Trial marks a milestone in personalized neuro-oncology. It proved that individualized mRNA neoantigen vaccines can be designed, manufactured, and administered in a clinically meaningful time frame—and can activate a tumor-specific immune response in glioblastoma patients, offering hope in a historically difficult-to-treat cancer.

See also:

• Glioblastoma
• Personalized mRNA Neoantigen Vaccine
• Neoantigen
• Cancer Vaccine for Glioma
• mRNA Vaccine Technology

Building upon the insights from NOA-16, subsequent research has aimed to enhance the therapeutic efficacy of IDH1-targeted vaccines. The AMPLIFY-NEOVAC trial is a notable example, designed to assess the combination of the IDH1 vaccine with a PD-L1 checkpoint inhibitor. This approach seeks to amplify the immune response by simultaneously targeting the tumor-specific antigen and modulating immune checkpoints.