Personalized cancer vaccine for patients with fusion-driven sarcomas

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

This study is testing a personalized cancer vaccine for patients with certain types of sarcomas to see if it can help their immune system fight the cancer and improve their chances of living longer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 2 Years to 40 Years
• Sex: All
• Sponsor: University Hospital Tuebingen (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 4 sites (Essen and 3 other locations)
• Trial ID: NCT06094101 on ClinicalTrials.gov

What this trial studies

The PerVision trial evaluates a personalized cancer vaccine designed for patients with metastasized fusion-driven sarcomas, including Ewing sarcoma, rhabdomyosarcoma, and synovial sarcoma. This interventional, multicenter, open-label study utilizes next-generation sequencing to identify specific tumor mutations and create a tailored peptide vaccine. The primary goals are to assess the safety of the vaccine and its ability to induce a T-cell immune response, as well as to gather data on its effects on event-free survival and overall survival. The study aims to provide insights that could be applicable to other tumor types as well.

Who should consider this trial

Good fit: Ideal candidates include patients with confirmed metastatic fusion-driven sarcomas who are in partial or complete remission after standard chemotherapy.

Not a fit: Patients who have not undergone prior chemotherapy or those with non-fusion-driven sarcomas may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to a novel treatment option that enhances immune response against specific sarcoma mutations, potentially improving patient outcomes.

How similar studies have performed: While personalized cancer vaccines are an emerging field, this specific approach targeting fusion-driven sarcomas is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria, definition of partial remission plus (PRplus)

* Screening Stage 1:

  * Confirmed metastatic fusion-driven rhabdomyosarcoma, Ewing- and synovial sarcoma in first or second complete remission (CR) or partial response (PR) after local therapy and intensive standard chemotherapy protocols.
  * Whole exome sequencing and RNA sequencing data of the gene fusion (fusion-breakpoint RNA sequence) must be available by registration to the INFORM (Individualized therapy for relapsed malignancies in childhood), MASTER (Register study Molecularly Aided Stratification for Tumor Eradication) or HEROES-AYA networks (Heterogeneity, evolution and resistance of fusion-driven sarcomas in AYA) or similar evaluation.
* Screening stage 2:

  * Design and production of the patient-individual vaccine cocktail was successful
  * Patients have reached a complete or stable partial remission (CR or PR) the end of adjuvant and/or maintenance cytotoxic treatment. Cytotoxic treatment as per standard or trial recommendations has been completed. Definition of PRplus: Partial remission(plus) implicates that all remaining tumor residua including all metastases have received local therapy by this time point: Either surgical removal or local irradiation. The assessment of which therapy modality and, in the case of irradiation, which radiation dose is selected, lies with the treating physician. Whether PRplus is achieved will be decided finally by the investigator after review of the patient records.

Exclusion Criteria:

* Ejection fraction \< 25%
* Creatinine-clearance \< 40ml/min
* Bilirubin \> 4mg/dl
* Alanine aminotransferase (ALT) \> 400 units (U)/l and/or aspartate aminotransferase (AST) \> 400 U/l
* Severe infection (Human immunodeficiency virus (HIV): positive for the presence of human immunodeficiency virus-1 or human immunodeficiency virus-2 (positive antigen/antibody or nucleic acid tests \[NAT\]) and CD4-positive cells \< 500/μl. Hepatitis B virus: positive for the presence of hepatitis B virus (positive for hepatitis B core antibody \[HBcAb\] or positive hepatitis B surface antigen \[HBsAg\]) and hepatitis B NAT test \> 2000 IU/ml). Hepatitis C virus: positive for heavy chain only antibody \[HCAb\] or for nucleic acid amplification testing (NAT). Other infections that, in the opinion of the investigator, do not allow a participation in the study.)
* Subjects with a known hypersensitivity / allergy to any component of the study drugs.
* Subjects who have received a live, attenuated vaccine within 28 days prior to the administration of the study drug (only stage 2).
* Subjects with a prior haematopoietic stem cell transplantation / prior organ transplantation.
* Patients suffering from other malignancies (with the exception of those with a negligible risk of metastasis or death and treated with curative outcome) within 5 years prior to study start.
* Current or anticipated need for any of the following medications interfering with T cell function from 14 days before 1st vaccination until 28 days after 1st vaccination: Immunosuppressive agents, which influence functionality and activity of T cells, such as steroids (more than 0,5 mg/kg body weight prednisolone-equivalent), calcineurin-inhibitors, mofetil mycophenolate, sirolimus, everolimus, and cytotoxic medication. Those drugs should be avoided until 28 days after third/final vaccination but may be given after discussion with the principal investigator. Application of tyrosine kinase inhibitors is permitted during the trial (only stage 2).
* Significant psychiatric disabilities that, in the judgment of the investigator, do not assure reliable participation in the present study.
* Uncontrolled seizure disorders (occurrence of at least one generalized seizure in the last 3 months) or severe peripheral neuropathy/leucoencephalopathy (\> grade 2 according to NCI CTCAE v5.0 neurotoxicity criteria).
* Autoimmune disease (e.g. idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, autoimmune dermatitis) requiring immunosuppressive treatment
* Pregnant females
* Female subjects of childbearing potential (postmenarcheal, with an intact uterus and at least one ovary, and less than one year postmenopausal) not agreeing to use acceptable method(s) of contraception from 30 days prior to Screening stage 2 visit to 180 days after the last vaccination.
* Male subjects of reproductive capacity not agreeing to use effective contraception from first vaccination of this study to 180 days after the last vaccination.
* Not willing and/or not able to comply with treatment plan, scheduled visits, laboratory tests, contraceptive guidelines and other study procedures.
* History of any illness or clinical condition that might confound the results of the study or pose an additional risk in administering study drug to the subject, according to the judgement of the investigator. This may include but is not limited to: history of central nervous system or cardiovascular disease, history of relevant drug allergies, history of psychiatric disorder, history or present of clinically significant pathology.
* Karnofsky performance status of \< 70% for subjects ≥ 16 years of age, Lansky performance status of \< 70% for subjects \< 16 years of age
* Participation or intended participation in another clinical phase I or II trial with an investigational drug or product within 28 days prior to enrollment (with the exception to participation of the "frontline and relapsed rhabdomyosarcoma study"( (FaR-RMS) after completion of the maintenance therapy (EudraCT-2018-000515-24)). Commonly used drugs as per standard or phase III-trials are permitted.

Where this trial is running

Essen and 3 other locations

• Pediatrics III, West German Cancer Centre, University Hospital — Essen, Germany (Not_yet_recruiting)
• Universitätsklinikum, Klinik für Kinder- und Jugendmedizin — Frankfurt am Main, Germany (Not_yet_recruiting)
• Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum — Freiburg im Breisgau, Germany (Not_yet_recruiting)
• University Children's Hostpital — Tübingen, Germany (Recruiting)

Study contacts

• Principal investigator: Martin Ebinger, Prof. Dr. — University children's hospital Tübingen
• Study coordinator: Martin Ebinger, Prof. Dr.

Conditions Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; metastasized fusion-driven sarcoma; clinical study; phase I/II