🧪 AMPLIFY-NEOVAC Trial [Neurosurgery Wiki]

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====== 🧪 AMPLIFY-NEOVAC Trial ======

The **AMPLIFY-NEOVAC [[Trial]]** is a Phase I [[multicenter]] [[clinical trial]] investigating the combination of an **[[IDH1 R132H]]-targeted [[peptide vaccine]]** with an **anti–PD-L1 immune checkpoint inhibitor** in patients with newly diagnosed **IDH1-mutant astrocytomas**.

===== 🎯 Objective =====

To evaluate the **safety**, **tolerability**, and **immunogenicity** of a **combination immunotherapy**:
  - **IDH1 R132H peptide vaccine** (used in the NOA-16 trial)
  - **Atezolizumab** (a PD-L1 immune checkpoint inhibitor)

===== 👥 Patient Population =====

  * Adults with newly diagnosed **WHO grade III or IV IDH1 R132H-mutant astrocytomas**
  * Must have completed **standard-of-care therapy** (surgery and radiotherapy)
  * Patients with or without prior temozolomide exposure may be included

===== 💉 Rationale =====

  * **NOA-16** showed the IDH1 R132H vaccine is safe and immunogenic
  * Adding a **PD-L1 inhibitor** may enhance T cell infiltration and sustain immune responses by preventing **T cell exhaustion**
  * The goal is to **amplify anti-tumor immunity** and improve long-term outcomes

===== 🔬 Study Design =====

  * **Open-label**, Phase I
  * Two arms:
    - **IDH1 vaccine alone**
    - **IDH1 vaccine + atezolizumab**
  * Evaluates:
    - Adverse events
    - Vaccine-specific T cell responses
    - Tumor progression-free survival (PFS)

===== 🔎 Key Points =====

  * **Atezolizumab** is already approved for several cancers (lung, bladder) and blocks PD-L1 → PD-1 signaling
  * The vaccine uses the same **20-mer peptide** from NOA-16, targeting the **IDH1 R132H mutation**
  * The trial will help determine if combining checkpoint blockade with vaccination **improves response durability**

===== 🚧 Challenges =====

  - Immune-related adverse events due to checkpoint inhibition
  - Blood-brain barrier may limit immune cell access
  - Small patient population (IDH1-mutant astrocytomas are rare)

===== 🔁 Connection to NOA-16 =====

  * NOA-16 demonstrated feasibility and immune activation using the IDH1 vaccine alone
  * AMPLIFY-NEOVAC builds on this by aiming to **strengthen and prolong** the anti-tumor immune response

===== 📌 Summary =====

The **AMPLIFY-NEOVAC Trial** is an important next step in **personalized [[glioma immunotherapy]]**, exploring whether **checkpoint blockade can synergize** with **neoantigen vaccination** to generate deeper, longer-lasting anti-tumor responses in patients with **IDH1 R132H-mutant gliomas**.

===== 🔗 Related Pages =====

  * [[NOA-16 Trial]]
  * [[IDH1 Mutation]]
  * [[Personalized mRNA Neoantigen Vaccine]]
  * [[Checkpoint Inhibitor]]
  * [[Cancer Vaccine for Glioma]]

If you're studying feasibility and safety of personalized vaccines → NOA-16 is essential.

If you're interested in advanced therapeutic strategies and combination immunotherapy → AMPLIFY-NEOVAC is more cutting-edge.
((Bunse L, Rupp AK, Poschke I, Bunse T, Lindner K, Wick A, Blobner J, Misch M, Tabatabai G, Glas M, Schnell O, Gempt J, Denk M, Reifenberger G, Bendszus M, Wuchter P, Steinbach JP, Wick W, Platten M. AMPLIFY-NEOVAC: a randomized, 3-arm multicenter phase I trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with an immune checkpoint inhibitor targeting programmed death-ligand 1 in isocitrate dehydrogenase 1 mutant gliomas. Neurol Res Pract. 2022 May 23;4(1):20. doi: 10.1186/s42466-022-00184-x. PMID: 35599302; PMCID: PMC9125855.))