Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy targeting mesothelin (MSLN) was active in patients with malignant pleural disease (MPD) from primary malignant pleural mesothelioma (MPM) with minimal toxicity, according to phase 1 data presented at the American Association for Cancer Research (AACR) Annual Meeting 2019.

MSLN is a cell surface antigen shown to be highly expressed in MPD, but has low expression in normal tissue. In this study, researchers tested CD28-costimulated MSLN CAR with the “safety switch” Icaspase-9 safety gene (IcasM28z) in 21 patients with MPD. Each patient was given a single dose intrapleurally with (18 individuals) or without cyclophosphamide preconditioning.

Although 1 patient had grade 3 febrile neutropenia related to cyclophosphamide, no patients had toxicities higher than grade 2 related to the CAR-T therapy.

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According to the study abstract, there were no on-target, off-tumor toxicities, according to abstract authors.

One patient was able to undergo curative-intent surgical resection 6 weeks after receiving the CAR-T infusion. And, once safety of the therapy was observed (6-17 weeks following CAR-T infusion), 14 patients were able to undergo off-protocol treatment with anti-PD1 checkpoint blockade.

Overall, the best response among 19 patients with MPM was complete metabolic response on PET scan in 2 patients, 5 patients with a partial response, and 4 with stable disease.

Because of this encouraging data, a trial of MSLN-targeted CAR-T plus anti-PD1 agents is planned for the second quarter of 2019.

Reference

  1. Adusumilli PS, Zauderer MG, Rusch VW, et al. A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: safety and efficacy. Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3, 2019; Abstract CT036.