Two recent studies demonstrated CAR T-cell therapy activity in certain types of solid tumors, according to results presented at the American Society of Clinical Oncology annual meeting. The CAR T cells used new targets outside of the CD19 targets used for the therapy’s current approvals in leukemia and lymphoma.
In the first study, a phase I trial, Adusumilli et al. used mesothelin-targeted CAR T cells combined with pembrolizumab, a PD-1 inhibitor, in 21 patients with previously treated pleural cancers that expressed mesothelin (19 with malignant pleural mesothelioma, 1 with metastatic lung cancer, and 1 with metastatic breast cancer). Thirteen patients had persistent CAR T cells during follow-up, and eight of those patients showed response (two durable complete remissions and six partial responses) for a 72% response rate.
Additionally, they found that the PD-1 inhibitor helped maintain the CAR T-cell response by rejuvenating the cells from tumor-induced exhaustion. They theorized that it may help expand CAR T-cell use to solid tumors.
Zhan et al., in the second phase I study, used claudin 18.2-targeted CAR T cells in 12 patients with metastatic adenocarcinoma (7 gastric and 5 pancreatic). Of those, one had a complete response, three had partial responses, and five had stable disease for an overall objective response rate of 33%. Plus, the treatment was well tolerated: no serious adverse events, treatment-related death, severe neurotoxicity, or grade 4 adverse events (except for decreased lymphocytes, neutrophils and white blood cells) occurred, and all cytokine release syndromes observed were grade 1 or 2.
Both groups of researchers said that the results were promising and that they hoped their findings may one day lead to new treatment options for solid tumors, but more in-depth clinical trials are needed.