Malignant pleural mesothelioma (MPM) is an uncommon but aggressive neoplasm with low survival rates. For patients with early stage resectable MPM the role of radical surgery remains controversial and multimodal treatment might improve patient prognosis. Dendritic cell therapy (DCT) with Mesopher proved to be safe and yielded promising results in patients with MPM, with single agent radiological activity, representing the rationale for a combined (neo)adjuvant approach with extended pleurectomy/decortication (eP/D) surgery.
This open label, single center, phase 1 study will evaluate the feasibility of DCT with Mesopher performed before and after eP/D in patients with resectable epithelioid MPM. Safety and immunological effects of (neo)adjuvant DCT will also be determined. Sixteen adult patients diagnosed with resectable epithelioid MPM will be enrolled following first-line chemotherapy. Before standard-of-care chemotherapy, a leukapheresis will be performed from which monocytes will be isolated and used for further differentiation into DCs. Hereafter, DCs will be loaded with allogeneic MPM tumor cell line lysate (Pheralys) and maturated using the Jonuleit cytokine cocktail. The subsequently formulated drug product (Mesopher) will be re-injected 4 weeks after completing chemotherapy, 2 times every other week. Four weeks after the first injection with DCT, patients will undergo eP/D surgery followed by three bi-weekly injections with DCT, starting 4 weeks after surgery. In total, five DC vaccinations will be administered. Tumor material will be collected before starting neo-adjuvant DCT and at time of surgery. Tumor-specific immune activation will be investigated using both tumor material and peripheral blood samples prior and post DCT with flow cytometry, imaging mass cytometry, and T-cell receptor repertoire analysis. The trial is active at the Erasmus MC, Rotterdam (NL), enrolling patients since January 2022.
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L. Cantini: Financial Interests, Personal and Institutional, Research Grant: ESMO. R. Cornelissen: Financial Interests, Personal, Invited Speaker: BMS, Roche, Pfizer, Boehringer Ingelheim, Novartis; Financial Interests, Personal, Advisory Role: Roche, MSD, Boehringer Ingelheim. D.W. Dumoulin: Financial Interests, Personal, Invited Speaker: BMS, Roche, Pfizer, Novartis. J.G. Aerts: Financial Interests, Personal and Institutional, Research Grant: Amphera, Eli Lilly, Roche; Financial Interests, Personal, Ownership Interest: Amphera; Financial Interests, Personal, Advisory Board: Amphera, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Takeda, Bayer, AstraZeneca, Roche. All other authors have declared no conflicts of interest.