Novel immunotherapy clinical trials in malignant pleural mesothelioma

Abstract

In this article, we review ongoing novel clinical trials currently investigating immunotherapeutic approaches for patients with malignant pleural mesothelioma (MPM). There is a dearth of effective therapeutic options for patients diagnosed with MPM and metastatic cancers of the pleura; these diseases have an estimated annual incidence of 150,000. Modulating the immune microenvironment to promote antitumor immune responses by systemically and regionally delivered therapeutic agents is an active area of investigation. We have conducted a review of the clinical trials database for clinical trials actively recruiting MPM patients. We focused on novel therapeutic agents administered either systemically or intrapleurally to modulate the tumor immune microenvironment. Herein, we have summarized the published results of early phase clinical trials. A total of 43 clinical trials met our inclusion criteria. These trials are investigating immunologic agents (n=20) and antibody directed therapies (n=23). The regional intrapleural delivery technique (6 trials) is used to administer chemotherapy agents (3 of 6 trials) and immunotherapy agents (3 of 6 trials), including chimeric antigen receptor T cells (1 of 6 trials). Current clinical trials modulating the MPM immune microenvironment and the combination of these novel agents with standard of care therapy provide a promising area of investigation for MPM therapy.

EURACAN/IASLC Proposals for Updating the Histologic Classification of Pleural Mesothelioma: Towards a More Multidisciplinary Approach

“…108 Mesothelin may also be a target for chimeric antigen receptor-modified T cells, given its frequent expression in mesotheliomas, especially the epithelioid subtype. [109][110][111] Recommendations. (1) Routine incorporation of the above biomarkers into standard reports is not recommended, but data should be accrued in a regulated manner within clinical trials and recorded in reports, if requested.…”

Overcoming tumor antigen heterogeneity in CAR-T cell therapy for malignant mesothelioma (MM)

“…The addition of the anti-angiogenic agent bevacizumab to pemetrexed/cisplatin chemotherapy improved MPM OS in selected patients from 16.1 to 18.8 months [7,8] , but has not been widely adopted. The multimodality treatment of surgery, radiotherapy, and pemetrexed/cisplatin chemotherapy has resulted in 5-year survival of only about 5% and is a viable option for only a small number of MPM patients [9,10] . MM's advanced stage, localization, and morphology contribute to its high resistance to therapy.…”