Study Shows CAR T-Cell Success in Solid Tumors

A phase I study presented at the American Association of Clinical Research Annual Meeting showed that chimeric antigen receptor (CAR) T-cells targeting mesothelin were active in patients with malignant pleural disease from mesothelioma and other solid tumors.

Researchers used a second-generation CD28-costimulated mesothelin CAR with the Icaspase-9 safety gene (IcasM28z). The study included 21 patients with biopsy-proven malignant pleural disease expressing mesothelin (19 with malignant pleural mesothelioma, 1 with lung cancer, and 1 with breast cancer). Patients received a single dose of IcasM28z CAR T-cells intrapleurally with or without cyclophosphamide preconditioning by either pleural catheter or an interventional radiology procedure.

Eighteen patients received cyclophosphamide pre-conditioning. Twelve patients were administered CAR T-cells using an interventional radiology procedure.

One patient experienced grade 3 febrile neutropenia related to cyclophosphamide use. The researchers did not observe CAR T-cell-related toxicities higher than grade 2.

Treatment response

One patient successfully underwent curative-intent surgical resection six weeks after CAR T-cell infusion. CAR T-cell persistence was reported in 13 patients. In these patients, the CAR T-cells persisted from day two to 42 weeks. T-cell persistence was associated with decreased serum soluble mesothelin-related peptide levels and evidence of tumor regression on imaging studies. The treatment yielded a 72% response rate when combined with immune checkpoint blockade.

Among the 19 patients with malignant pleural mesothelioma, two experienced complete metabolic response on positron emission tomography scan, five achieved partial response, and four had stable disease.