Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1-Based Therapy : Final Results from a Phase 2 Study
Krebs, M.G. (Manchester Academic Health Science Centre)
Forster, M. (UCL Cancer Institute/UCL Hospitals NHS Foundation)
Majem Tarruella, Margarita (Institut de Recerca Sant Pau)
Peguero, J.
Iams, W. (Vanderbilt Ingram Cancer Center Division of Hematology/Oncology)
Clay, T. (St. John of God Subiaco Hospital)
Roxburgh, P. (Wolfson Wohl Cancer Research Centre)
Doger, B. (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
Bajaj, P. (Tasman Oncology)
Barba Joaquin, Andrés (Institut de Recerca Sant Pau)
Perera, S. (Clinical Development. Immutep GmbH)
Mueller, C. (Clinical Development. Immutep GmbH)
Triebel, F. (Research and Development. Immutep S.A.S.)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Introduction: Eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, triggers antigen-presenting cell and T-cell (CD4 and CD8) activation and helps overcome resistance to programmed cell death protein 1 or programmed cell death-ligand 1 (PD-(L)1) inhibitors. We assessed efti plus pembrolizumab in second-line anti-PD-(L)1-refractory metastatic patients with NSCLC. Methods: After confirmed progression on anti-PD-(L)1-based first-line therapy, patients received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles and then every 3 weeks for up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary endpoint was the objective response rate by modified Response Evaluation Criteria in Solid Tumors version 1. 1 for immune-based therapies. Secondary endpoints included disease control rate, progression-free survival, overall survival (OS), and tolerability. Exploratory endpoints included tumor growth kinetics and predefined subgroup analyses. Programmed cell death-ligand 1 tumor proportion score was assessed centrally. Results: Thirty-six patients were enrolled from April 2019 to August 2021 using Simon's two-stage design. Most patients (81. 8%) had low or negative (<50%) PD-(L)1 tumor proportion score. First-line therapy was anti-PD-(L)1-based for all patients, combined with chemotherapy for 66. 7%. The confirmed objective response and disease control rates were 8. 3% and 33. 3%. The median progression-free survival was 2. 1 months and the median OS was 9. 9 months. Patients exhibiting high PD-(L)1 expression or acquired resistance to PD-(L)1 inhibitors revealed superior response and survival outcomes, and OS was closely correlated with disease control. No treatment-emergent adverse event led to permanent discontinuation of study treatment. Conclusions: Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Anti-PD-(L)1 Refractory ; Eftilagimod alpha ; Immune checkpoint inhibitor ; Non-small cell lung cancer ; Pembrolizumab
Publicat a:	JTO Clinical and Research Reports, Vol. 5 Núm. 11 (november 2024) , p. 100725, ISSN 2666-3643

DOI: 10.1016/j.jtocrr.2024.100725
PMID: 39403626

11 p, 744.6 KB

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