Journal article
Safety and Tolerability of Letetresgene Autoleucel (Lete-cel; GSK3377794): Pilot Studies in Patients With Advanced Non-Small Cell Lung Cancer
Clinical cancer research, Vol.31(3), pp.529-542
02/03/2025
DOI: 10.1158/1078-0432.CCR-24-1591
PMCID: PMC11788651
PMID: 39576208
Abstract
To evaluate safety, tolerability, and anti-tumor response of lete-cel, genetically modified autologous T-cells expressing a T-cell receptor specific for NY-ESO-1/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in human leukocyte antigen HLA-A*02-positive (HLA-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-) patients with New York esophageal squamous cell carcinoma 1 (NY-ESO-1)- and/or LAGE-1a-positive non-small cell lung cancer (NSCLC).
Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multi-arm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent NSCLC.
Over 2500 patients were screened for target expression. In the multi-arm study, 738 (45%) of 1638 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 (AEs) were reported in either study. Cytopenias and cytokine release syndrome were the most common treatment-emergent AEs. Combining pembrolizumab with lete-cel did not appear to increase toxicity over lete-cel alone. Limited anti-tumor 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.
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. Anti-tumor activity was observed in a limited number of patients.
Details
- Title: Subtitle
- Safety and Tolerability of Letetresgene Autoleucel (Lete-cel; GSK3377794): Pilot Studies in Patients With Advanced Non-Small Cell Lung Cancer
- Creators
- Mehmet Altan - The University of Texas MD Anderson Cancer CenterGilberto Lopes - Sylvester Comprehensive Cancer CenterT Jeroen N Hiltermann - University Medical Center GroningenRamaswamy Govindan - Washington University in St. LouisLiza C Villaruz - UPMC Hillman Cancer CenterEmiliano CalvoMartin J Edelman - Fox Chase Cancer CenterMuhammad Furqan - University of IowaJoel Neal - Stanford UniversityEnriqueta Felip - Vall d'Hebron Hospital UniversitariJennifer W Carlisle - Emory UniversityJohn V Heymach - The University of Texas MD Anderson Cancer CenterRóisín Eilish O'Cearbhaill - Memorial Sloan Kettering Cancer CenterMarjorie Zauderer - Westchester Medical CenterMichael Chisamore - Merck & Co., Inc., Rahway, NJ, USAEllie Corigliano - GlaxoSmithKlineIoanna Eleftheriadou - GlaxoSmithKlineStefan Zajic - GlaxoSmithKlineBen Jenkins - Institute of Cancer ResearchSophia Goodison - GlaxoSmithKlineSunil Suchindran - GlaxoSmithKlineNatalia Ramos-Hernandez - GlaxoSmithKlineNidale Tarek - GlaxoSmithKlineAdam J Schoenfeld - Memorial Sloan Kettering Cancer Center
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.31(3), pp.529-542
- DOI
- 10.1158/1078-0432.CCR-24-1591
- PMID
- 39576208
- PMCID
- PMC11788651
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Publisher
- AMER ASSOC CANCER RESEARCH; PHILADELPHIA
- Grant note
- GSK: 208749/208471
The authors would like to thank the patients, their families, and all investigators involved in this study. Special thanks to others involved in the design and conduct of the study at GSK, including Athanasia (Nancy) Skoura, Benedetto Farsaci, Jimson D'Souza, Thomas Faitg, Yi Hsing, Bryan Barnes, Colleen Valenzuela, Ale Bozac, Sheila Walker, Allison Hainline. Medical writing support was provided by Jessica Men, PharmD, and editorial support was provided by Travis Taylor, BA, both of Scion (a division of Prime), supported by GSK according to Good Publication Practice guidelines (Link). These studies were sponsored by GSK (study IDs: 208749/208471).
- Language
- English
- Electronic publication date
- 11/22/2024
- Date published
- 02/03/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984751759902771
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