New CAR T-Cell Targets Show Safe Results in Early Clinical Trials
Findings from two phase I clinical trials presented at the American Association for Cancer Research 2019 annual meeting indicate that targeting CAR T cells against mesothelin for advanced solid tumors (https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1291) and HER2 for advanced sarcoma is safe and shows clinical antitumor activity (https://www.aacr.org/Newsroom/Pages/News-Release-Detail.aspx?ItemID=1292).
Researchers in the first study used mesothelin-targeted CAR T cells in 21 patients with malignant pleural disease (i.e., malignant pleural mesothelioma, metastatic lung cancer, and metastatic breast cancer). Of those, 13 patients had persistent CAR T cells measured in peripheral blood and experienced more than a 50% decrease in the levels of a mesothelin-related peptide and measurable tumor regression on imaging studies.
After receiving CAR T-cell infusions, 14 patients also were treated with anti-PD1 checkpoint blockade agents, which have been found to reactivate exhausted CAR T cells. After 21 cycles, two patients had complete metabolic response, five had partial response, and four had stable disease. The researchers said that additional studies are needed to determine the treatment’s long-term efficacy.
Researchers in the second study treated 10 patients aged 4-54 with refractory or metastatic HER2-positive sarcoma (i.e., osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, and synovial sarcoma) with HER2-targeted CAR T cells. The cells were detectable in all patients six weeks after infusions.
Two patients had complete responses, three had stable disease, and five had progressive disease. The researchers noted that the treatment-related toxicities noted with other HER2-targeted therapies, such as cardiopulmonary dysfunction, were not seen with the CAR T-cell treatment.
Larger follow-up studies are needed to define the efficacy and optimal dosages.