Safety and tolerability of letetresgene autoleucel (GSK3377794): Pilot studies in patients with advanced non–small cell lung cancer Journal Article
| Authors: | Altan, M.; Lopes, G.; Hiltermann, T. N. J.; Govindan, R.; Villaruz, L. C.; Calvo, E.; Edelman, M. J.; Furqan, M.; Neal, J.; Felip, E.; Carlisle, J. W.; Heymach, J. V.; O’Cearbhaill, R. E.; Zauderer, M.; Chisamore, M.; Corigliano, E.; Eleftheriadou, I.; Zajic, S.; Jenkins, B.; Goodison, S.; Suchindran, S.; Ramos-Hernandez, N.; Tarek, N.; Schoenfeld, A. J. |
| Article Title: | Safety and tolerability of letetresgene autoleucel (GSK3377794): Pilot studies in patients with advanced non–small cell lung cancer |
| Abstract: | 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. ©2024 The Authors. |
| Keywords: | adult; human tissue; protein expression; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; cancer surgery; overall survival; genetics; fludarabine; clinical trial; drug tolerability; drug efficacy; drug safety; chemotherapy; cancer staging; neurotoxicity; neoplasm staging; antigen expression; t lymphocyte; progression free survival; neutrophil count; phase 2 clinical trial; anemia; nausea; carcinoma, non-small-cell lung; lung neoplasms; membrane proteins; cyclophosphamide; kidney failure; antineoplastic activity; pathology; tumor antigen; carcinogenesis; monoclonal antibody; pneumonia; lung tumor; hypotension; t lymphocyte receptor; immunology; antigens, neoplasm; cancer vaccine; cancer vaccines; pilot study; pilot projects; multicenter study; epitope; ctag1b protein, human; membrane protein; graft versus host reaction; brain disease; pancytopenia; real time polymerase chain reaction; phase 1 clinical trial; mesna; drug therapy; cytopenia; disease exacerbation; adoptive immunotherapy; immunotherapy, adoptive; esophageal squamous cell carcinoma; hla a2 antigen; hla-a2 antigen; recurrence free survival; non small cell lung cancer; tumor microenvironment; adverse event; leukapheresis; respiratory distress; guillain barre syndrome; cytokine release syndrome; procedures; tocilizumab; antibodies, monoclonal, humanized; very elderly; intention to treat analysis; humans; human; male; female; priority journal; article; pembrolizumab; letetresgene autoleucel; acute febrile encephalopathy |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 3 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-02-01 |
| Start Page: | 529 |
| End Page: | 542 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-1591 |
| PUBMED: | 39576208 |
| PROVIDER: | scopus |
| PMCID: | PMC11788651 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Adam J. Schoenfeld -- Source: Scopus |
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