Safety and Tolerability of Letetresgene Autoleucel (GSK3377794): Pilot Studies in Patients with Advanced Non-Small Cell Lung Cancer.

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

Patients and methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

Results: More than 2,500 patients were screened for target expression. In the multiarm study, 738 (45%) of 1,638 tested patients were HLA-A*02-positive. NY-ESO-1 and LAGE-1a testing was positive in 12% (62/525) and 4% (15/348) of tested patients, respectively. Forty-one patients positive for HLA-A*02 and antigen expression were screened in the single-arm study. Overall, 43 patients underwent leukapheresis and 18 received lete-cel across studies. Lete-cel demonstrated a manageable safety profile. No fatal treatment-related serious adverse events (AE) were reported in either study. Cytopenias and cytokine release syndrome were the most common treatment-emergent AEs. Combining pembrolizumab with lete-cel did not seem to increase toxicity over lete-cel alone. Limited antitumor activity was observed; one of 18 patients had a durable response persisting for 18 months. Pharmacokinetic data showed similar T-cell expansion in all patients.

Conclusions: Extensive HLA-A*02 and antigen expression testing was performed to identify potential participants. Lete-cel was generally well tolerated and had no unexpected AEs. Antitumor activity was observed in a limited number of patients.