Immune Microenvironment and Gene Expression Profiling in Mesothelioma
NCT Number: NCT06581549
Acronym: Imaging-Meso
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Mesothelioma|Mesotheliomas Pleural|Mesothelioma; Lung
Sponsor: Istituto Oncologico Veneto IRCCS
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 220
Study Design: Observational Model: |Time Perspective: p
Start Date: 2023-11-02
Completion Date: 2026-12-31

Summary:
Pleural and peritoneal mesotheliomas (PPM) are rare cancers mostly related to asbestos-exposure, which are characterized by a complex histopathological diagnosis and staging, few therapeutic options and a dismal prognosis. The main unmet medical need in PPM is the lack of a treatment sequence for affected patients. The advent of immune checkpoint inhibitors has changed the first line treatment of PPM, thanks to the improvement in survival achieved by the combination of ipilimumab and nivolumab that are currently approved for non-epithelioid histology in our Country.

PPM is characterized by a large heterogeneity of the genomic landscape, which is mainly characterized by the loss of tumour suppressor genes and mutations in DNA repair genes and by an "altered- suppressed" or "excluded" tumor immune microenvironment (TIME).

The goal of this project is to improve the immune-biological and molecular stratification of PPM subgroups that can lead to the identification of different personalized treatment approaches. PPM patients (N=220) will be retrospectively (N=150) and prospectively (N=70) recruited from the coordinator center and 6 participating Italian centers. Treatment-naïve tumor samples will be collected and analyzed by bulk gene expression and spatial whole transcriptome analysis, and by 9-color multiplex immunofluorescence.

New targets or actionable pathways potentially emerging from such studies will be finally assessed and validated in patient-derived organoids/xenografts that accurately reflect PPM tumorigenesis.

Primary Outcome Measures: Primary outcome, PPM treatment-naïve tumor samples and classification in different clusters according to the differential expression of molecular and gene signatures by Gene expression profile (GEP) analysis., Through study completion, an average of 3 years|Primary outcome, Identification of molecular and immune signatures predictive of resistance or sensitivity to systemic anticancer drugs: chemotherapy or immunotherapy administered as first line treatment by spatial whole transcriptome analysis., Through study completion, an average of 3 years|Primary outcome, PPM surgical specimens and comparison with GEP in matched treatment-naïve tumor samples will be performed by gene expression profile analysis with GEP analysis., Through study completion, an average of 3 years
Secondary Outcome Measures: Secondary outcome, Characterization and quantification of immune cell distribution and their spatial relationships in treatment naïve tumor samples of PPM patients will be performed by a 9-color multiplex immunofluorescence (mIF) analysis., Through study completion, an average of 3 years|Secondary outcome, Immune phenotypes defined by mIF and the immune signatures identified by GEP analyses will be performed in each treatment-naïve tumor sample., Through study completion, an average of 3 years
Other Outcome Measures: Third outcome, In vitro and in vivo models of PPM for the investigation of activated signatures, new therapeutic targets and drug sensitivity tests. will be performed by:

* development of in vitro 'organ-like' 3D structures (PDOs) derived from patient tumor tissue;
* patient-derived xenograft (PDX) from PPM patients;
* matched comparison of histological and molecular features of PDOs and PDXs with the original tumor tissues;
* drug sensitivity/resistance tests in vitro and in vivo., Through study completion, an average of 3 years