Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
AI Summary:
Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-L1 inhibitors.AI Topics:
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.
Krebs, Matthew G.
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
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See full publications listForster, Martin
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listMajem, Margarita
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listPeguero, Julio
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listIams, Wade
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listClay, Tim
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listRoxburgh, Patricia
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
Drew, Yvette and Kim, Jae-Weon and Penson, Richard T. and O'Malley, David M. and Parkinson, Christine and Roxburgh, Patricia and Plummer, Ruth and Im, Seock-Ah and Imbimbo, Martina and Ferguson, Michelle and Rosengarten, Ora and Steeghs, Neeltje and Kim, Min Hwan and Gal-Yam, Einav and Tsoref, Daliah and Kim, Jae-Hoon and You, Benoit and De Jonge, Maja and Lalisang, Roy and Gort, Eelke and Bastian, Sara and Meyer, Kassondra and Feeney, Laura and Baker, Nigel and Ah-See, Mei-Lin and Domchek, Susan M. and Banerjee, Susana (2024) Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study. Clinical Cancer Research, 30 (1). pp. 50-62. ISSN 1078-0432
See full publications listDoger, Bernard
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listBajaj, Pawan
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listBarba, Andres
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listPerera, Suvini
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listMueller, Christian
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
See full publications listTriebel, Frédéric
Author
Krebs, Matthew G. and Forster, Martin and Majem, Margarita and Peguero, Julio and Iams, Wade and Clay, Tim and Roxburgh, Patricia and Doger, Bernard and Bajaj, Pawan and Barba, Andres and Perera, Suvini and Mueller, Christian and Triebel, Frédéric (2024) 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, 5 (11): 100725. ISSN 2666-3643
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