Soluble LAG-3 protein eftilagimod alpha combined with pembrolizumab shows promising clinical efficacy as first-line treatment for advanced or metastatic NSCLC.

Lymphocyte activation gene 3 (LAG3) is expressed on multiple cell types, including CD4⁺ and CD8⁺ T cells and Treg cells, and is required for optimal T-cell regulation and homeostasis.¹ Persistent antigen stimulation in cancer or chronic infection leads to chronic LAG3 expression, promoting T-cell exhaustion. Eftilagimod alpha is a soluble LAG-3 protein and acts by binding to a major histocompatibility complex on antigen-presenting cells. Eftilagimod alpha also upregulates the expression of key biological molecules, including interferon-γ and CXCL10, which boost the immune system’s ability to fight cancer.

The phase 2 TACTI-002 trial (NCT03625323) explored the clinical efficacy of the combination of eftilagimod alpha and pembrolizumab as first-line treatment in one subcohort of participants with metastatic NSCLC. Dr. Enric Carcereny of the Catalan Institute of Oncology, Spain, presented the results.²

A total of 114 treatment-naïve participants with advanced or metastatic NSCLC were treated with eftilagimod alpha plus pembrolizumab for 8 cycles, followed by 16 cycles of pembrolizumab monotherapy. About one-third of participants presented with PD-L1 expression (according to the tumor proportion score) below 1%, and 42% of participants showed PD-L1 expression in the 1%-49% range. “Cumulatively, about 75% of participants had PD-L1 expression below 50%,” said Dr. Carcereny.

The median overall survival (mOS) was 20.2 months (95% CI, 14.4-35.5 months). Second-line therapy, mostly chemotherapy-based, was given to 35% of participants. mOS was related to PD-L1 expression status: 15.5 months in participants with <1% PD-L1 expression, 23.4 months in participants with 1%-49% PD-L1 expression, and not yet reached in participants with >50% PD-L1 expression. The median progression-free survival was 6.6 months (95% CI, 4.6-9.8 months) and the median duration of response was 21.6 months (95% CI, 14.4-24.4 months).

“Eftilagimod alpha combined with pembrolizumab and without platinum-based chemotherapy backbone showed promising clinical efficacy in participants with treatment-naïve NSCLC and should be investigated further,” concluded Dr. Carcereny.

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