SOHO 2026 Annual Meeting

INTRODUCTION

•AML patients unfit for intensive chemotherapy and allo-HCT receiving HMA-based therapy achieve ~60% initial response, but ~70% relapse with high mortality

• Low tumor mutation burden, shared antigen expression between leukemic and healthy cells, and immunosuppressive milieu have impeded immunotherapy efforts

•Personalized neoantigen vaccination with mRNA and peptide vaccines has recently been shown to be immunogenic and potentially improve patient outcomes [1-3]

•Alternative neoantigen resources like splicing and fusion neoantigens could be utilized to overcome low TMB

•Several driver mutations of AML (NPM1, FLT3, IDH2) have been shown to be immunogenic

•HMAs have been shown to upregulate several leukemia associated antigens [4]

• Personalized peptide-based neoantigen vaccination could offer a promising strategy to induce antitumor immunity and it has been untested in AML

AIM

To determine the safety, tolerability, and feasibility of MYELOVAC, a peptide-based vaccine platform combining shared leukemia-associated antigens (LAAs) with patient-specific neoantigens, in AML patients in first complete remission (CR1) after HMA-based therapy

VACCINE DESIGN:

Integrates four antigen sources:

• Shared LAAs targeting WT1 [5], PRAME [6], and Cyclin A1 [7]

•Personalized neoantigens from somatic mutations, splicing events, and gene fusions

•Adapts the PGV001 platform (safe and immunogenic in solid cancers and myeloma). Administered with poly-ICLC and Montanide adjuvants concurrently with HMA-based therapy.

STUDY DESIGN

• Single-center phase I trial

• Pre-enroll at diagnosis: tissue banking (BM aspirate + skin biopsy) + neoantigen ID

• Vaccination begins at confirmed CR1

• DLTs assessed across two 28-day windows

• Schedule: 4 shared doses/2mo → 6 personalized doses/4mo → 4 combined monthly doses

Patients

• Adults ≥18 with AML, unfit for intensive chemo and HCT

• Achieving CR/CRi; planned HMA-based therapy; can be MRD positive

• ECOG 0-3; active autoimmune disease past 1 yr excluded

• Target enrollment: N=10

Endpoints

• Primary: DLT rate (safe if ≤2/10 DLTs)

• Secondary: feasibility, immunogenicity (IFN-γ ELISPOT, ICS stainining), MRD conversion (flow/PCR), RFS and OS at 18 months

•Exploratory: Bone marrow microenvironment changes before and after vaccination (scRNA seq, TCR seq, comparison of ongoing remission samples and relapse samples with baseline)

CONCLUSIONS

MYELOVAC is the first personalized neoantigen peptide vaccine effort for AML

• Targets multiple antigen classes combined with HMA-based therapy, which may enhance immune priming and improve vaccine response

• Aims to inform vaccination efforts in AML; enrollment anticipated early 2027

ACKNOWLEDGEMENTS

This study is supported by the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai. We deeply thank Robert Horwitz for his generous philanthropic support to the study

CONTACT INFORMATION

Nikolaos .spyrou@mountsinai.org

John.Mascarenhas@mssm.edu

REFERENCES

[1] Saxena et al, Cancer Discovery, 2025

[2] Saxena et al, Nat Med, 2025

[3] Saxena et al, Nat Rev Cancer, 2021

[4] Wong et al, Front Oncol, 2021

[5] Jamy et al, Future Oncol, 2025

[6] Yang et al, Front Immunol, 2024

[7] Leung et al, Blood Adv, 2020

SOHO 2026 Annual Meeting

MYELOVAC: A Phase 1 Trial of a Personalized Peptide-Based Neoantigen Vaccination Platform in Combination With Hypomethylating Agent-Based Therapy for Patients With Acute Myeloid Leukemia in First Complete Remission Ineligible for Intensive Chemotherapy and Allogeneic Stem Cell Transplantation

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