PNV21 vaccine / Fred Hutchinson Cancer Center - LARVOL DELTA

A personalized neoantigen vaccine induces anti-tumor T cell responses in patients with PD-1/PD-L1 inhibitor refractory metastatic melanoma (SITC 2025) - "This phase I study evaluated the immunologic impact of the neoantigen peptide vaccine PNV-021 in PD-1-refractory melanoma.Methods Eight patients received up to 20 neoantigen peptides, predicted to bind HLA class I/II, every four weeks alongside Poly-ICLC and nivolumab. b) Week 12 biopsies from all patients showed increased CD163+ macrophage and CD3+ T cell infiltration compared to enrollment biopsiesAbstract 602 Figure 2Request permissionsUniform Manifold Approximation and Projection (UMAP) of the phenotypic distribution of tumor-reactive T cells. Tumor-reactive TCRs expressed genes associated with T cell activation and exhaustion, including the previously characterized tumor-reactive T cell signature markers CXCL13 and ENTPD1"

Clinical • IO biomarker • Metastases • Tumor-specific neoantigens • Melanoma • Oncology • Solid Tumor • CD163 • CDC37 • CXCL13 • DCT • ENTPD1 • ERN1 • HSP90AB1 • IFNG • PRAME • Tyrosinase

A phase I clinical trial of a personalized neoantigen vaccine in PD-1 inhibitor refractory metastatic melanoma (SITC 2025) - "Increases in tumor immune infiltration was observed in both responding and non-responding patients.Conclusions PNV-21, a personalized neoantigen peptide vaccine, combined with nivolumab and weekly Poly-ICLC, was demonstrated to be well tolerated and safe. Furthermore, the treatment led to anti-tumor immune activation and objective responses in heavily pretreated patients with metastatic melanoma. Vaccine-induced immune responses were detectable in patients with and without objective clinical benefit.Acknowledgements Funding for this trial was provided by Amazon, and we would llike to thank patients and their families.Ethics Approval The study was approved by the Fred Hutchinson Cancer Center IRB (approval number RG1121642).Abstract 608 Figure 1Request permissionsRegression of large tumor following vaccination in patient 6, residual tumor negative for melanoma by pathology of biopsy at 6 monthsAbstract 608 Figure 2Request permissionsRECIST changes from baseline, numbers..."

Clinical • Metastases • P1 data • Tumor-specific neoantigens • Melanoma • Oncology • Solid Tumor • CD4 • CD8 • TLR3

Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Nov 2026 ➔ Nov 2027 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Breast Cancer • Cutaneous Melanoma • Eye Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Mucosal Melanoma • Non Small Cell Lung Cancer • Ocular Melanoma • Oncology • Solid Tumor • BRAF • ER • HER-2 • PGR

Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma or Hormone Receptor Positive Her2 Negative Metastatic Refractory Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Nov 2025 ➔ Nov 2026 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Cutaneous Melanoma • Eye Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Mucosal Melanoma • Ocular Melanoma • Oncology • Solid Tumor • BRAF • ER • HER-2 • PGR

Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma or Hormone Receptor Positive Her2 Negative Metastatic Refractory Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Nov 2024 ➔ Nov 2025

Metastases • Trial completion date • Breast Cancer • Cutaneous Melanoma • Eye Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Mucosal Melanoma • Ocular Melanoma • Oncology • Solid Tumor • BRAF • ER • HER-2 • PGR