Malignant Pleural Mesothelioma

P2, N=40, Recruiting, Istituto Oncologico Veneto IRCCS | Not yet recruiting --> Recruiting

P3, N=53, Active, not recruiting, Ferring Ventures Limited | Trial completion date: Nov 2024 --> Apr 2026 | Trial primary completion date: Nov 2023 --> Mar 2024

P2, N=58, Active, not recruiting, The Netherlands Cancer Institute | Trial completion date: Mar 2025 --> Mar 2026

The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

This study characterized CD146 expression and binding/internalization kinetics of the CD146-targeting antibody OI-3 coupled with 212Pb (212Pb-TCMC-OI-3) in human mesothelioma cells...The ability of 212Pb-TCMC-mOI-3 to target and inhibit the growth of intraperitoneal mesothelioma xenografts supports targeted radionuclide therapy's efficacy for metastatic peritoneal mesothelioma. This study highlights the potential of localized CD146-targeted radioimmunotherapy for malignant mesothelioma, offering a new avenue for improving patient outcomes.

P2, N=106, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.

HPD is a mode of progression for ICI-treated PM patients. Further investigation is needed to better define and anticipate HPD in these patients.

Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers.

Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma.

P1/2, N=49, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

P=N/A, N=52, Recruiting, Centro di Riferimento Oncologico - Aviano

SMRP is a promising serum biomarker for predicting survival in MPM patients treated with ICT and warrants prospective investigation.

Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased (P<0.05) . Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.

By integrating genomic analysis with a series of in vitro and in vivo functional studies, we validate and prioritize several non-oncogene addictions conferred by CDK7, CHK1, HDAC3, RAD51, TPX2, and UBA1 as targetable vulnerabilities, revealing previously unappreciated aspects of PM biology. Our findings support the growing consensus that stress-responsive non-oncogenic signaling plays a key role in the initiation and progression of PM and provide a functional blueprint for the development of unprecedented targeted therapies to combat this formidable disease.

P2, N=41, Completed, Sellas Life Sciences Group | N=31 --> 41

Moreover, the adeno-associated virus serotype 6 (AAV6) has been engineered to deliver both NF2 and SuperHippo genes into mesothelial cells, which substantially impedes tumor growth in xenograft and genetic DPM models and prolongs the median survival of mice. These findings serve as a proof of concept for the potential use of gene therapy targeting the Hippo pathway to treat DPM.

With its emergence as a predictive biomarker, the implementation of MTAP IHC into diagnostic routine for NSCLC and other tumors is likely to take place soon. In this review article, we summarize the current literature on the role of MTAP in thoracic tumors and evaluate different testing methods, including IHC, FISH and next generation sequencing.

P1/2, N=91, Recruiting, NuCana plc | Trial primary completion date: Aug 2024 --> Jan 2025

The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes. This review article provides an overview of epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and genetic markers), staging, and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery, chemotherapy, immunotherapy, and radiotherapy. It also sheds light on some recent studies (EMPHACIS, CALGB30901, Checkmate-743, etc.) that have led to significant developments in recent years with clinically meaningful results.

Furthermore, when we tested Neratinib (an inhibitor of MAD2L1) and iMDK (an inhibitor of MDK) we found that they are effective on MPM cells, in part phenocopying the effects of MAD2L1 and MDK gene silencing. In summary, in the present work, we report that BAG2, MAD2L1, and MDK are bona fide cancer-driver genes for MPM worth of further studies.

Notably, high LAT1 expression proved to be a significant predictor of outcome, particularly in the subgroup with high PLR and SII. LAT1 was a significant predictor of outcomes in patients with PM and was more predictive of worse outcomes in patients with high inflammatory and low nutritional status.

P2, N=40, Not yet recruiting, Istituto Oncologico Veneto IRCCS | Trial completion date: Dec 2026 --> Mar 2027 | Initiation date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jun 2026 --> Mar 2026

P1/2, N=56, Active, not recruiting, Aminex Therapeutics, Inc. | Suspended --> Active, not recruiting

P1, N=5, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=16 --> 5 | Trial completion date: Mar 2025 --> Jan 2026 | Trial primary completion date: Mar 2025 --> Feb 2024

P2, N=47, Completed, Fundación GECP | Recruiting --> Completed | Trial completion date: Apr 2025 --> Feb 2024 | Trial primary completion date: Mar 2025 --> Feb 2024

During her clinical history, radiological images presented an unusual representation of the disease, with a pseudo progression discussed many times by several specialists. The patient's overall survival improved as a result of the multidisciplinary team and the availability of medicines outside of clinical practice.

P=N/A, N=220, Recruiting, Istituto Oncologico Veneto IRCCS

The numeric difference in PFS between treatment groups was not statistically significant, likely related to a smaller than planned sample size. High levels of soluble mesothelin should potentially be considered to select against the use of mesothelin-targeting therapies in development that are neutralized by soluble mesothelin.

P2, N=40, Completed, Ain Shams University | Recruiting --> Completed | Trial completion date: Dec 2024 --> Apr 2024

P1/2, N=52, Recruiting, Baylor College of Medicine | Not yet recruiting --> Recruiting

P=N/A, N=200, Recruiting, Mayo Clinic | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Well-differentiated papillary peritoneal mesothelial tumors were primarily incidental findings. There was no WDPMT-related mortality, so there was no distinct role for routine cytoreductive surgery or systemic therapy. Genomic profiles can help to differentiate WDPMT from DPM and PM.

P1/2, N=56, Suspended, Aminex Therapeutics, Inc. | Recruiting --> Suspended

P1, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Dec 2025 | Trial primary completion date: Apr 2024 --> Dec 2025

Implementing these strategies requires overcoming challenges in patient selection, combination therapies, biomarker identification, and cost considerations. Collaboration is crucial for transforming these insights into impactful clinical interventions, heralding the era of personalized and precision medicine for PM.

P1/2, N=56, Recruiting, Aminex Therapeutics, Inc. | Phase classification: P1b/2a --> P1/2 | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

P1, N=10, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

These results suggest that ONX-0914 prevents the internal destructive cleavage of WT1235 by IP, thereby promoting the specific presentation of the WT1 epitope by MESO-4. In conclusion, selective IP inhibitors might offer a means to modulate cancer cell immunogenicity by directing the presentation of particular tumor epitopes.

P2, N=102, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: May 2024 --> Dec 2024

The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge...The cytidine analog capecitabine and its metabolite 5'-deoxy-5-fluorocytidine (5'-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism...In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.

To our knowledge, this is the second reported case of dual immunotherapy used as first-line in MPM with a major clinical response. To investigate the clinical outcome, we conducted additional molecular analyses of the MPM tumor and we reviewed the literature on immunotherapy in MPM to discuss the role of PD-L1 and BAP1.

P1, N=54, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Jul 2024 | Trial primary completion date: Mar 2025 --> Nov 2023