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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, Matthew G Forster, M. Majem, M. Peguero, J. Iams, W. Clay, T. Roxburgh, P. Doger, B. Bajaj, P. Barba, A.
Krebs, Matthew G
Forster, M.
Majem, M.
Peguero, J.
Iams, W.
Clay, T.
Roxburgh, P.
Doger, B.
Bajaj, P.
Barba, A.
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Abstract
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.
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2024
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Article
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Krebs MG, Forster M, Majem M, Peguero J, Iams W, Clay T, et al. 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. JTO clinical and research reports. 2024 Nov;5(11):100725. PubMed PMID: 39403626. Pubmed Central PMCID: PMC11472608. Epub 2024/10/15. eng.