A recent ongoing study has tested Mesothelin-targeted (CAR) T-cell Therapy and it showed efficacy within the phase one of the trials, in patients with mesothelioma, pleural disease, breast cancer, non-small cell lung cancer. Followed by PD-1 checkpoint inhibition treatment showed better results with hard-to-treat solid tumors. The results have been announced at American Society of Gene and Cell Therapy 2018 Annual Meeting.
Mesothelin is a beneficial therapeutic target as its presence is not observed on normal mesothelial cells. It is a cell-surface antigen that helps in differentiating tumors and is present in many cancers such as pancreatic, lung, pleural, breast, ovarian and mesothelioma itself.
13 patients have been treated in the phase 1 trial of the study, infused with mesothelin targeted iCasM28z CAR T-cell therapy. Single doses varying from 3×105 cells/kg to 1×107 cells/kg of CAR T-cell therapy were given across six cohorts. Cohort from 2 to 6 was also preconditioned with 1.5 g/m2 intravenous cyclophosphamide. 11 out of 13 patients are alive still. One patient out of the 10 which received cyclophosphamide showed a full metabolic response and one other patient showed a partial response. Three of these patients had stabilized the disease. 8 out of the 10 patients had CAR t-cells in their peripheral blood.
Clinical AEs (adverse events) included pleuritis, pericarditis and peritonitis with 1 patient developing grade 3 febrile neutropenia induced by cyclophosphamide.
Bases on preclinical pieces of evidence, 6 patients were treated with subsequent PD-L1/PD-1 checkpoint inhibition treatment. All of these patients are still alive at the data cutoff. One of these 6 patients showed a full metabolic response, two experienced partial response, one acquired stabilized disease, with 2 patients experiencing progressive disease. Five of these patients didn’t undergo any following therapies with the presence of CAR T-cell still observed in their peripheral blood. No serious AEs exceeding grade 2 have been noticed following anti-PD-1 Therapy.
The efficacy of this treatment has been pointed out in 73-years old mesothelioma patient by Abdusumilli (principal investigator in the study). He received 3×105 cells/kg dose of iCasM28z CAR T-cell therapy with cyclophosphamide, followed by Keytruda. He has experienced full metabolic response with the presence of CAR T-cells in peripheral blood and tissue even by the end of 32 weeks. The patient has not undergone any subsequent treatments even after approximately a year.
Hence, this therapy portrays early signs of efficacy in the treatment of cancers with mesothelin tumor-differentiation antigen.