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Clinical trials

INTERCEPT H3 - A Multicenter Phase I Peptide Vaccine Trial to Exploit Neoepitope-Specific T Cells for the treatment of H3-Mutated Gliomas; status: open

The INTERCEPT H3 trial combines H3K27M peptide vaccination with radiotherapy and checkpoint inhibitor treatment in patients with diffuse midline gliomas.

Contribution of IMU: Coordination of sample logisitics and collection, training of external labs, processing of PBMC, serum, plasma, CSF and tumor for immune assays, including IFNγ ELISpot assays for immunogenicity assessment (primary endpoint), flow-cytometry, ELISA and TCR repertoire analysis for secondary endpoints and translational research.

NECVAX-NEO1-LT An open-label, phase I monocenter, clinical trial of NECVAX-NEO1
in addition to anti-PD-1 or anti-PD-L1 monoclonal antibody checkpoint inhibitor monotherapy in patients with solid tumors; status: recruiting

This trial makes use of a patient-individual salmonella Ty21a carrier-based DNA plasmid vaccine that can be orally administered and enrolls patients of different tumor entities.

Contribution of IMU: Training of external labs, logistic of PBMC collection, evaluation of antigen-specific T cell responses.

AMPLIVY NEOVAC (NOA-21) AMPLIFYing NEOepitope-specific VACcine Responses in progressive diffuse glioma – a randomized, open label, 3 arm multicenter Phase I trial to assess safety, tolerability and immunogenicity of IDH1R132H-specific peptide vaccine in combination with checkpoint inhibitor Avelumab; Status: recruiting

The trial will address safety and tolerability of the combination of the IDH1R132H-specific vaccine with checkpoint blockade and seeks to explore predictive biomarkers for response to checkpoint blockade in post-treatment tumor tissue.

Contribution of IMU: Tumor, PBMC, serum and plasma processing for IFNᵞ-ELISpot assays and anti-IDHR132H-ELISA as part of the secondary endpoint analysis; cytokine screening, flow cytometric profiling of immune cell subsets and TCR repertoire analysis for evaluation of explorative endpoints and translational research. Coordination of sample logistics and distribution.

INFORM-NIVENT - exploratory multinational phase I/II combination study of Nivolumab and Entinostat in children and adolescents with refractory high-risk malignancies; status: recruiting
 
The aim of this trial is to determine preliminary activity of the combination treatment with nivolumab and entinostat in children and adolescents with high risk refractory/relapsed/progressive tumors harboring a high mutational load, high PD-L1 mRNA expression or focal MYC(N) amplification and explore activity in biomarker low tumors (low mutational load, low PD-L1 mRNA expression and non-MYC(N) amplified)

Contribution of IMU: PBMC, serum and plasma isolation, flow cytometric analysis of immune biomarkers in fresh blood samples, multiplexed cytokine profiling, coordination of sample logistics and distribution.

VXM01-AVE-04-INT An open-label, Phase I/II multicenter clinical trial of VXM01 in combination with avelumab to evaluate safety and efficacy in patients with progressive glioblastoma following standard treatment, with or without second surgery; status: recruitment closed
 
A multicenter phase I/II trial to evaluate the efficacy and safety combining oral T cell vaccination targeting VEGRF2 (VXM01) with anti-PD-L1 checkpoint inhibitor therapy (Avelumab) in recurrent Glioblastoma patients following tumor resection and radiochemotherapy containing temozolomide.
 
Contribution of IMU: Processing of PBMC, and tissue samples as part of the exploratory endpoint analysis. IFN-γ ELIspot, flow cytometry Immunophenotyping and TCR repertoire profiling to monitor vaccine induced T cell responses.

FORCE Fostering efficacy of anti – PD-1 – treatment: Nivolumab plus radiotherapy in advanced NSCLC, Open label phase II trial; status: recruitment closed

AIO-YMO/TRK-0415 (FORCE) is a Phase 2, open-label of nivolumab, patients with metastatic non-squamous NSCLC with the necessity of radiotherapy of a metastatic site (e.g. bone) in 2nd-line or 3rd-line treatment for study group A and patients with metastatic non-squamous NSCLC without the necessity of radiotherapy in 2nd-line or 3rd-line treatment for study Group B.

Contribution of IMU: PBMC, serum and plasma isolation, IFNγ-ELISpot Assay, FACS of checkpoint Inhibitory molecules, Luminex and TCR sequencing as part of the accompanying translational research.

NOA-16 Targeting IDH1R132H in WHO grade III-IV IDH1R132Hmutated gliomas by a peptide vaccine – a Phase I safety, tolerability and immunogenicity multicenter trial (EudraCT 2014-000503-27)
Status: closed. See Platten et al., Nature 2021 (https://pubmed.ncbi.nlm.nih.gov/33762734/) for results.
 
The NOA-16 trial is the first-in-man trial of the IDH1 (isocitrate dehydrogenase type 1) peptide vaccine targeting the IDH1R132H mutation (amino acid exchange from arginine to glutamine at position 132 of IDH1). The aim of this trial is to evaluate the safety and tolerability of and immune response to the IDH1 peptide vaccine in patients with IDH1R132H-mutated, WHO grade III-IV gliomas.
 
Contribution of IMU: PBMC, serum and plasma processing for and IFNγ-ELISpot assay and IDH1R132H antibody response via ELISA as part of the primary endpoint analysis.

POSITIVE III Physical exercise program in lung cancer patients with non-operable disease undergoing palliative treatment - Lung Cancer Study; status: recruitment closed

Patients with advanced stage non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) often experience multidimensional impairments, affecting quality of life during their course of disease. In lung cancer patients with operable disease, several studies have shown that exercise has a positive impact on quality of life and physical functioning. There is limited evidence regarding efficacy for advanced lung cancer patients undergoing palliative treatment. Therefore, the POSITIVE study aims to evaluate the benefit of a 24-week exercise intervention during palliative treatment in a randomized controlled setting.

Contribution of IMU: PBMC, serum and plasma processing for and IFNᵞ-ELISpot assays, Cytokine screening and Treg FACS as part of the secondary endpoint analysis.

TNBC-MERIT / BN_0002-01 RNA Vaccination of breast tumor patients; status: recruitment closed

The Mutanome Engineered RNA Immuno-Therapy (MERIT) study introduces a novel concept for Individualized Cancer Immunotherapy (IVAC®) to treat each patient with the relevant and immunogenic RNA vaccines for a given patient's tumour. The TNBC-MERIT trial uses two complementary strategies, the IVAC® WAREHOUSE and the IVAC® MUTANOME concept, resulting in two custom-made IVAC® investigational medicinal products (IMPs) (IVAC_W_bre1_uID and IVAC_M_uID) for each individual patient.

Contribution of IMU: PBMC processing as part of the secondary endpoint analysis.

RADIMMUNE - A randomized phase II study of radiation induced immune boost in operable non-small cell lung cancer, status: recruitment closed

The goal of this randomized trial is to assess if a preoperative single fraction low-dose radiation is able to improve anti-tumor immune response in operable early stage lung cancer.

Contribution of IMU: Tissue collection and dissociation, in vitro expansion and flow cytometric analysis of tumor-infiltrating lymphocytes, TCR repertoire analysis.

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