Integration of the PD-L1 inhibitor atezolizumab and WT1/DC vaccination into standard-of-care first-line treatment for patients with epithelioid malignant pleural mesothelioma-Protocol of the Immuno-MESODEC study

Our plain-English summary of Integration of the PD-L1 inhibitor atezolizumab and WT1/DC vaccination into standard-of-care first-line treatment for patients with epithelioid malignant pleural mesothelioma-Protocol of the Immuno-MESODEC study, by J. Van den Bossche, M. De Laere, K. Deschepper, et al (PloS One, 2024).

The study

• Authors: J. Van den Bossche, M. De Laere, K. Deschepper, P. Germonpré, Y. Valcke, J. Lamont, B. Stein, K. Van Camp, C. Germonpré, G. Nijs, E. Roelant, S. Anguille, E. Lion, Z. Berneman
• Journal: PloS One
• Published: 2024;19(7):e0307204
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms' tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8-10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8-10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial's primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.

Copyright: © 2024 Van den Bossche et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

In plain English

This article is a study protocol. It described the plan for a clinical trial and reported no results from that trial. The authors designed the Immuno-MESODEC study, a multicenter, single-arm, phase I/II trial, to test whether two immune-based treatments could be added safely and practically to standard first-line chemotherapy for epithelioid malignant pleural mesothelioma. The trial aimed to enrol 15 evaluable patients whose cancer had not been treated before and could not be removed by surgery. Patients were to receive cisplatin (75 mg/m2) and pemetrexed (500 mg/m2) chemotherapy together with the anti-PD-L1 antibody atezolizumab (1200 mg). They were also to receive a vaccine made from their own dendritic cells. Messenger RNA (mRNA) for the Wilms' tumor 1 (WT1) protein was introduced into these cells by electroporation. The authors stated that if this combination proved feasible and safe, it should be studied further. They noted that any results on how well the treatment works would need to be interpreted with caution, because the trial is small and has no control group within the study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Study protocol for an academic, multicenter, single-arm, phase I/II clinical trial whose main aims are safety and feasibility. No results are reported.
• Who was studied: Planned: 15 evaluable, previously untreated patients with unresectable epithelioid subtype malignant pleural mesothelioma (MPM). A patient counts as evaluable after completing at least the first chemo-immunotherapy cycle.
• Exposure: This is a treatment trial; asbestos exposure was not studied. The treatment is standard chemotherapy (cisplatin 75 mg/m2 and pemetrexed 500 mg/m2) plus the anti-PD-L1 antibody atezolizumab (1200 mg). It also includes an autologous dendritic cell vaccine in which WT1 mRNA is introduced into the cells by electroporation (WT1/DC). Treatment is given over four 3-weekly cycles.
• The authors' conclusion: The authors stated that the trial will evaluate whether the combination is feasible and safe, and that if so, it should be investigated further as a treatment option.
• Limitations the authors state:
  • The authors stated that efficacy results will need to be interpreted with caution because of the small sample size and the lack of a control arm within the study.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: PD-L1, Atezolizumab (Tecentriq), Epithelioid, Pleural Mesothelioma, Prognosis, Chemotherapy, Immunotherapy, Pemetrexed (Alimta).

Related studies

• WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome — Z.N. Berneman, M. De Laere, et al. (2025)
• CX-072 (pacmilimab), a Probody PD-L1 inhibitor, in combination with ipilimumab in patients with advanced solid tumors (PROCLAIM-CX-072): a first-in-human, dose-finding study — R.E. Sanborn, O. Hamid, et al. (2021)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• A gut microbiota rheostat forecasts responsiveness to PD-L1 and VEGF blockade in mesothelioma — M. Zhang, A. Bzura, et al. (2024)
• Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial — P.S. Kok, P.M. Forde, et al. (2022)
• Impressive clinical response to anti-PD-1 therapy in epithelioid mesothelioma with high clonal PD-L1 expression and EML4-ALK rearrangement — G. Bronte, A. Delmonte, et al. (2020)

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