Generation of frameshift-mutated TGFβR2-specific T cells in healthy subjects following administration with cancer vaccine candidate FMPV-1/GM-CSF in a phase 1 study

• Published in: Cancer Immunology, Immunotherapy : CII Vol. 74; no. 4; pp. 115 - 10
• Main Authors: Inderberg, Else Marit, Singh, Nand, Miller, Robert, Arbe-Barnes, Sarah, Eriksen, Henrik K., lversen, Berit, Juul, Hedvig Vidarsdotter, Eriksen, Jon Amund, Handeland, Karianne Risberg
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 25.02.2025; Springer Nature B.V; Springer
• Subjects: Adult; Cancer; Cancer Research; Cancer vaccines; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Colony-stimulating factor; Frameshift Mutation; GM-CSF; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Healthy Volunteers; Humans; Hypersensitivity (delayed); Immune response; Immune response (cell-mediated); Immunology; Immunotherapy; Injection; Lymphocytes; Lymphocytes T; Lynch syndrome; Male; Medicine; Medicine & Public Health; Memory cells; Microsatellite instability; Middle Aged; Mutants; Mutation; Neoplasms - immunology; Oncology; Peptide vaccine; Receptor, Transforming Growth Factor-beta Type II - genetics; Receptor, Transforming Growth Factor-beta Type II - immunology; Skin tests; T-Lymphocytes - immunology; TGFβR2; Transforming growth factor-b; Vaccines; Young Adult; TGFβR2; Immune response; Peptide vaccine; GM-CSF; Immunotherapy; Lynch syndrome
• ISSN: 1432-0851; 0340-7004; 1432-0851
• DOI: 10.1007/s00262-025-03969-6

FMPV-1 is a component of FMPV-3, an investigational cancer-specific vaccine and being developed to activate anti-cancer T cell responses targeting frameshift mutations of MSI-H cancers. FMPV-1 is designed to activate T cell responses against transforming growth factor β receptor 2 (TGFβR2) frameshift mutation. Microsatellite instability high (MSI-H) gastrointestinal cancers frequently harbour TGFβR2 frameshift mutations. This first-in-human, phase 1, single centre, open-label study included 16 healthy male subjects who received FMPV-1 (0.15 mg/injection) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.03 mg/injection) as two separate, co-located, injections on Days 1, 8, 15, 29 and 43. All subjects were followed to Day 365. A FMPV-1-specific delayed type hypersensitivity (DTH) skin reactivity test was performed with FMPV-1 (without GM-CSF) on Days 1, 29 and 43 with assessment after 2 days. All subjects were DTH negative at baseline, 8/16 were positive on Day 31 and 15/16 were positive on Day 45. Furthermore, the FMPV-1/GM-CSF induced frameshift mutant TGFβR2-specific T cells after the short vaccination period, and specific T cells were still detectable after 6 and 12 months indicating induction of frameshift mutant TGFβR2-specific T memory cells. Adverse events were limited to mild injection site reactions with no evidence of related systemic signs or symptoms. No other clinically important changes to vital signs, electrocardiograms, haematological, coagulation or laboratory measures related to treatment were observed. FMPV-1/GM-CSF was well tolerated and generated vaccine-specific T cell immune responses in healthy subjects. These findings support clinical studies in patients with, or at risk of, cancers carrying TGFβR2 frameshift mutations. Clinical trial identification : ClinicalTrials.gov: NCT05238558. EudraCT: 2020-004363-80.