927P Initial results from a phase II study (TACTI-002) of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab as 2nd line treatment for PD-L1 unselected metastatic head and neck cancer patients

Förster, Martin; Felip, Enriqueta; Doger, Bernard; Pousa, Antonio López; Carcereny, Enric; Bajaj, Pawan; Church, Matt; Peguero, Julio Antonio; Roxburgh, Patricia; Triebel, Frédéric

doi:10.1016/j.annonc.2020.08.1042

Cited by 7 publications

(7 citation statements)

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“…Eftilagimod alpha (Efti, IMP321, or LAG-3Ig) is a soluble LAG-3 fusion protein composed of the extracellular domain of LAG-3 and the Fc region of IgG that may activate antigenpresenting cells (DCs) through major histocompatibility complex (MHC)-II-mediated signaling; this activation results in an increase in interleukin (IL)-12 and tumor necrosis factor (TNF) levels and upregulation of CD80 and CD86 expression, along with the removal of the inhibitory effect of DCs on T cells through LAG-3 (16)(17)(18). The phase III TACTI-002 clinical trial (NCT03625323) used Eftilagimod alpha in combination with pembrolizumab as the first-line treatment for advanced tumors and metastatic NSCLC (part A) (19) and as second-line treatment for NSCLC (refractory to PD-1/PD-L1) (part B) and metastatic head and neck cancer (platinum-resistant) (part C) (20). Based on preliminary efficacy data, the FDA awarded the soluble LAG-3 protein eftilagimod alpha fast-track designation in April 2021; the phase II TACTI-003 study was conducted on LAG-3Ig combined with pembrolizumab as the first-line treatment for head and neck squamous cell carcinoma, while the INSIGHT-004 study is an ongoing study on LAG-3Ig combined with avelumab for the treatment of a variety of advanced solid tumors.…”

Section: Targeting Immune Checkpointsmentioning

confidence: 99%

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Bai

Cui

2022

Front. Immunol.

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Tumor immune microenvironment is a very complex system that is influenced by a wide range of factors; in this microenvironment, various immune cells, stromal cells, and cytokines can interact with tumor cells and jointly regulate this complex ecosystem. During tumor development, the tumor microenvironment (TME) shows the upregulation of inhibitory signals and downregulation of activating signals, which result in an immunosuppressive microenvironment and lead to tumor immune escape. In recent years, a variety of precision immunotherapy strategies have been developed to remodel the TME into a positive immune microenvironment by stimulating or restoring the inherent tumor inhibition ability of the immune system so as to improve anti-tumor therapeutic efficacy. This review focuses on immunotherapy strategies targeting the TME, including those that target the microenvironment to inhibit signaling, activate signaling, and specifically involve many new targets such as physical barriers, immune cells and their surface molecular receptors, cytokines, and metabolic factors. Furthermore, it summarizes the challenges faced while conducting research on the tumor immune microenvironment and the corresponding solutions.

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Section: Targeting Immune Checkpointsmentioning

confidence: 99%

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Bai

Cui

2022

Front. Immunol.

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“…The median duration of response (DOR) in the initial therapy for those with NSCLC was 21.6 months, whereas the median PFS was 6.6 months ( 131 ). The objective response rate (ORR) for a combination of treatments in the second-line therapy for individuals suffering from PD-L1-nonselective HNSCC was 39% ( 132 ). Tebotelimab (MGD013) is a tetravalent DART molecule meant for studies.…”

Section: Discussionmentioning

confidence: 99%

Bibliometric analysis of evolutionary trajectory and prospective directions of LAG-3 in cancer

Wang,

Zhang

et al. 2024

Front. Immunol.

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ObjectivesPerform a bibliometric analysis on the role of LAG-3 in the domain of cancer, elucidate the prevailing areas of research, and visually depict the evolutionary trajectory and prospective directions of LAG-3 research over the past twenty-three decades.Materials and methodsBetween 2000 and 2023, a comprehensive review of scholarly articles pertaining to LAG-3 research in the context of cancer was carried out using the Web of Science Core Collection (WoSCC) database. Bibliometric analysis can be conducted by taking advantage of VOSviewer (version 1.6.16) and CiteSpace (version 6.2.R4). Create a network diagram to visually represent various authors, countries, and organizations while assessing the publishing years, journals, references, and keywords.ResultsIn conclusion, 1841 records were identified and published in 587 publications. These records were authored by 12,849 individuals affiliated with 2491 institutes across 74 countries. There has been a substantial surge in publications subsequent to 2013. The USA, China, and Germany gave the majority of records, amounting to 69.69%. American institutions actively engage in collaboration with institutions located in other countries. Triebel, F., Vignali, Dario A. A., Workman, Creg J. Drake, Charles G., and Elkord, Eyad are highly regarded authors in their respective fields. However, it is worth noting that Triebel exhibits limited collaboration with other writers. The examination of the role of LAG-3 in cancer and its potential for use in clinical settings is a discernible trend, as seen by keyword analysis.ConclusionThe scientific interest in and attention towards LAG-3 has experienced a significant rise since 2013. The United States is leading the way, with China following closely behind. Promoting collaboration among writers, nations, and institutions with varied backgrounds is imperative. The discipline of immunotherapy is currently seeing ongoing progress. A thorough investigation of the distinctive cis ligand TCR-CD3 complex of LAG-3 and its signal transduction mechanism is necessary. Additionally, it is worthwhile to explore novel combinations of LAG-3 therapy.

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“…Eftilagimod alpha is a soluble agonist of the protein encoded by the LAG-3 gene that binds to a subset of the major histocompatibility complex class II molecules, facilitating the activation of antigen-presenting cells (APCs) and the recruitment and activation of CD4 and CD8 T cells. With an ORR of 36%, a phase II study evaluated the activity of eftilagimod alpha with pembrolizumab in the second line (36 patients) and presented encouraging results ( 119 ).…”

Section: The Emerging Role Of Target and Combination Therapymentioning

confidence: 99%

Multimodality treatment in recurrent/metastatic squamous cell carcinoma of head and neck: current therapy, challenges, and future perspectives

Pannunzio,

Di Bello,

Occhipinti

et al. 2024

Front. Oncol.

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Squamous cell carcinoma of the head and neck is a complex group of diseases that presents a challenge to the clinician. The prognosis in the recurrent/metastatic disease is particularly dismal, with a median survival of approximately 12 months. Recently, the personalized and multimodal approach has increased prognosis by integrating locoregional strategies (salvage surgery and stereotactic radiotherapy) and systemic treatments (chemotherapy, immunotherapy, and target therapy). Malnutrition is a significant clinical problem that interferes with dose intensity, and thus, feeding supplementation is critical not only to increase the quality of life but also to improve overall survival. With this review, we want to emphasize the importance of the multidisciplinary approach, quality of life, and nutritional supportive care and to integrate the latest updates of predictive biomarkers for immunotherapy and future therapeutic strategies.

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927P Initial results from a phase II study (TACTI-002) of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab as 2nd line treatment for PD-L1 unselected metastatic head and neck cancer patients

Abstract: Real-world data in the era of immune checkpoint inhibitors (ICIs): Cetuximab-containing first-line therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

Cited by 7 publications

References 0 publications

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Development of Immunotherapy Strategies Targeting Tumor Microenvironment Is Fiercely Ongoing

Bibliometric analysis of evolutionary trajectory and prospective directions of LAG-3 in cancer

Multimodality treatment in recurrent/metastatic squamous cell carcinoma of head and neck: current therapy, challenges, and future perspectives

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