Atara’s collaborator presents Phase 1 study results in Advanced Mesothelioma

Atara Biotherapeutics announced that the company’s collaborators at Memorial Sloan Kettering Cancer Center presented encouraging results from an ongoing MSK investigator-sponsored Phase 1 clinical study of a mesothelin-targeted CAR T immunotherapy for patients with mesothelin-associated malignant pleural solid tumors, primarily mesothelioma, who progressed following prior standard platinum-containing chemotherapy. Mesothelin-targeted, autologous CAR T cells delivered regionally were well-tolerated and showed anti-tumor activity in combination with pembrolizumab, a PD-1 checkpoint inhibitor. The Phase 1 clinical study recruited 21 patients, 19 with malignant pleural mesothelioma, one with metastatic lung cancer and one with metastatic breast cancer, who received a median of 3 prior treatment regimens, to evaluate the safety and potential anti-tumor activity of a CD28-costimulated, mesothelin-targeted autologous CAR T immunotherapy. The study included six dose cohorts with administration directly to the tumor site using regional delivery techniques, initially at a low CAR T dose without lymphodepleting chemotherapy, followed by increasing CAR T dose cohorts with lymphodepletion. A subset of these patients was subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor. Mesothelin-targeted, autologous CAR T administration was found to be generally well-tolerated with no CAR T-related toxicities higher than grade 2 observed based on monitoring multiple clinical, radiological, and laboratory parameters. CAR T cells were found to be persistent in the peripheral blood for 13 of the 21 patients during the 38-week evaluation, and their presence was associated with evidence of tumor regression on imaging studies. Best overall response rate for a subset of 11 MPM patients with minimum follow-up time of 3 months who also received pembrolizumab and lymphodepleting chemotherapy was 72% including 2 durable complete metabolic responses on PET imaging and 6 partial responses. Six of the 11 patients in this subset were programmed cell death ligand 1 negative, defined as undetectable expression of PD-L1 in tumor cells by immunohistochemistry, with 4 of the 8 total responses observed in PD-L1 negative patients. Following progression on standard platinum-containing chemotherapy, the expected ORR for patients with MPM treated with a checkpoint inhibitor is estimated between 5%-29% with one patient achieving a CR across multiple studies. MSK is also investigating mesothelin-targeted CAR T cells for patients with mesothelin-associated advanced breast cancer. Additional results from these ongoing studies are expected to be presented at upcoming scientific congresses.

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