NCT06094101

Personalized Vaccination in Fusion+ Sarcoma Patients (PerVision)

Prospective Phase I/II Trial of an Individualized Peptide Vaccine in Pediatric and AYA Patients with Metastasized Fusion-driven Sarcomas Following Standard Treatment

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: University Hospital Tuebingen · Academic / Other
• Sex: All
• Age: 2 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

The PerVision trial utilizes an approach of a patient-individual cancer vaccine with sarcoma-specific peptides in metastasized fusion-driven sarcoma patients determined by next generation whole exome sequencing of tumor and normal tissue as well as RNA sequencing of the tumor. This approach is applicable to all patients independent of the expression of distinct tumor associated antigens, and independent of their human leukocyte antigen-typing (HLA-typing). The results of this study can directly be translated to other tumor entities. It is an interventional, multicenter, open-label, phase I/II feasibility and early proof of concept study evaluating a personalized peptide vaccine. Primary objective is to evaluate safety and success of treatment, the latter be defined as vaccination-induced T-cell response without unacceptable toxicity.

Detailed description

The PerVision trial utilizes an approach of a patient-individual cancer vaccine with sarcoma-specific peptides (one peptide derived from the sarcoma-specific fusion breakpoint, 'fusion-peptide', and a second peptide derived from neoantigens derived from patient-specific non-synonymous mutations with the highest prediction score, 'mutation-based neopeptide') in metastasized fusion-driven sarcoma patients determined by next generation whole exome sequencing of tumor and normal tissue as well as RNA sequencing of the tumor. This approach is applicable to all patients independent of the expression of distinct tumor associated antigens, and independent of their human leukocyte antigen-typing (HLA-typing). The results of this study can directly be translated to other tumor entities. It is an interventional, multicenter, open-label, phase I/II feasibility and early proof of concept study evaluating a personalized peptide vaccine and the toll like receptor (TLR) 1/2 ligand XS15 emulsified in Montanide ISA 51 VG in fusion driven sarcoma patients. The principal questions are: 1. To investigate, whether it is possible to induce a mutation-specific immune response in sarcoma patients and young adults after salvage chemotherapy 2. To investigate possible side effects and toxicity of the treatment 3. To gather indications if our approach has a beneficial effect on residual disease as well as event free survival (EFS) of the patients. EFS and overall survival (OS) data will be compared within this single arm study to non-vaccinated patients of a historic control cohort. Patients will be recruited through the Society for Pediatric Oncology/Hematology (GPOH) networks Cooperative Soft Tissue Sarcoma Group (CWS) and Cooperative Ewing Sarcoma Group (CESS) and through the "Deutsches Konsortium für Translationale Krebsforschung" (DKTK) programs MASTER and INFORM as well as HEROES-AYA. For the screening phase, n=30 patients will be recruited, n=23 patients should be treated with at least one vaccine dose, with a drop-out rate we need n=21 patients for sufficient statistical power. Primary objective is to evaluate the safety, toxicity and in vivo immunological effects of a patient-individualized peptide vaccination (IPX vaccine) in patients with primary or relapsed metastasized fusion-driven sarcoma (FDS, rhabdomyosarcoma, Ewing- and synovial sarcoma) with an age ≥ 2 to \< 40 years in first or second complete remission or stable partial remission. Primary endpoint is "success of treatment", defined as the patient showing a vaccination-induced T cell response without unacceptable toxicity until Follow-up visit (28 ± 7 days after last vaccination).

Conditions

• Ewing Sarcoma
• Rhabdomyosarcoma
• Synovial Sarcoma

Interventions

Type	Name	Description
BIOLOGICAL	Peptide vaccine IPX	Peptide vaccine is a combination of 1. class II peptide spanning the sarcoma-specific fusion-breakpoint (fusion-peptide) 2. class-II neopeptide based on a patient-individual nonsynonymous mutation with a high immunogenicity (mutation-based neopeptide). 3. control peptide derived from Survivin. 4. adjuvant: toll like receptor (TLR) 1/2 ligand XS15.

Timeline

• Start date: 2023-09-19
• Primary completion: 2027-06-01
• Completion: 2027-09-01
• First posted: 2023-10-23
• Last updated: 2024-12-12

Locations

4 sites across 1 country: Germany