====== 🧪 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**.

===== 🧬 Overview =====

  * **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
((Platten M, Bunse L, Wick W. Emerging targets for anticancer vaccination: IDH. ESMO Open. 2021 Aug;6(4):100214. doi: 10.1016/j.esmoop.2021.100214. Epub 2021 Jul 13. PMID: 34271312; PMCID: PMC8287141.))

===== 🎯 Purpose =====

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.

===== 👥 Patient Population =====

  * 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

===== 💉 Intervention =====

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

===== ✅ Key Findings =====

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

===== 🔬 Significance =====

  * 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

===== 🚧 Limitations =====

  * 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

===== 🧾 Summary =====

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.