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Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to
Matthew G Krebs1, Martin Forster2, Margarita Majem3
1Division of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
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.
Insights
Eftilagimod alpha combined with pembrolizumab showed antitumor activity in patients with non-small cell lung cancer (NSCLC) resistant to PD-(L)1 inhibitors. This combination therapy was well-tolerated and warrants further investigation in NSCLC treatment.
Area of Science:
- Immunotherapy
- Oncology
- Clinical Trials
Background:
- Eftilagimod alpha (efti) is a soluble LAG-3 protein that activates immune cells and can overcome resistance to PD-(L)1 inhibitors.
- Patients with metastatic NSCLC often develop resistance to PD-(L)1 inhibitors, necessitating alternative treatment strategies.
Purpose of the Study:
- To assess the efficacy and tolerability of eftilagimod alpha plus pembrolizumab in patients with metastatic NSCLC who progressed on prior anti-PD-(L)1 therapy.
- To evaluate objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Main Methods:
- A phase II clinical trial enrolled 36 patients with anti-PD-(L)1-refractory metastatic NSCLC.
- Patients received efti (30 mg SC every 2 weeks for 8 cycles, then every 3 weeks) plus pembrolizumab (200 mg IV every 3 weeks).
- Primary endpoint was ORR; secondary endpoints included DCR, PFS, OS, and tolerability.
Main Results:
- The confirmed ORR was 8.3% and DCR was 33.3%.
- Median PFS was 2.1 months and median OS was 9.9 months.
- Patients with high PD-(L)1 expression or acquired resistance showed superior outcomes; no treatment-emergent adverse events led to permanent discontinuation.
Conclusions:
- Eftilagimod alpha plus pembrolizumab demonstrated antitumor activity and was well-tolerated in NSCLC patients resistant to PD-(L)1 inhibitors.
- The combination warrants further investigation for this patient population.
- Clinical trial NCT03625323.
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