Combination of paclitaxel and a LAG-3 fusion protein (eftilagimod alpha), as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Final results from the run-in phase of a placebo-controlled randomized phase II.

Duhoux, François; Jager, Agnes; Dirix, Luc; Huizing, Manon; Jérusalem, Guy; Vuylsteke, Peter; Cuypere, Eveline De; Breiner, Doris; Mueller, Christian; Brignone, Chrystelle; Triebel, Frédéric

doi:10.1200/jco.2018.36.15_suppl.1050

Cited by 14 publications

(8 citation statements)

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“…Combination of LAG‐3 blockade with chemotherapy in a phase‐I clinical trial has shown objective response rate up to 50%. Unexpectedly, this combination generates steady and sustainable APC niches maintaining T‐cell activation 238,239 . Of note, LAG‐3 also synergizes with PD‐1 in the regulation of CD8 + CTL exhaustion.…”

Section: Development Of T‐cell Exhaustionmentioning

confidence: 99%

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Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Hossain

Liu

Dai

et al. 2020

Medicinal Research Reviews

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Immunotherapy has revolutionized the treatment of cancer in recent years and achieved overall success and long‐term clinical benefit in patients with a wide variety of cancer types. However, there is still a large proportion of patients exhibiting limited or no responses to immunotherapeutic strategy, some of which were even observed with hyperprogressive disease. One major obstacle restricting the efficacy is that tumor‐reactive CD8+ T cells, which are central for tumor control, undergo exhaustion, and lose their ability to eliminate cancer cells after infiltrating into the strongly immunosuppressive tumor microenvironment. Thus, as a potential therapeutic rationale in the development of cancer immunotherapy, targeting or reinvigorating exhausted CD8+ T cells has been attracting much interest. Hitherto, both intrinsic and extrinsic mechanisms that govern CD8+ T‐cell exhaustion have been explored. Specifically, the transcriptional and epigenetic landscapes have been depicted utilizing single‐cell RNA sequencing or mass cytometry (CyTOF). In addition, cellular metabolism dictating the tumor‐infiltrating CD8+ T‐cell fate is currently under investigation. A series of clinical trials are being carried out to further establish the current strategies targeting CD8+ T‐cell exhaustion. Taken together, despite the proven benefit of immunotherapy in cancer patients, additional efforts are still needed to fully circumvent limitations of exhausted T cells in the treatment. In this review, we will focus on the current cellular and molecular understanding of metabolic changes, epigenetic remodeling, and transcriptional regulation in CD8+ T‐cell exhaustion and describe hypothetical treatment approaches based on immunotherapy aiming at reinvigorating exhausted CD8+ T cells.

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Section: Development Of T‐cell Exhaustionmentioning

confidence: 99%

“…Unexpectedly, this combination generates steady and sustainable APC niches maintaining T-cell activation. 238,239 Of note, LAG-3 also synergizes with PD-1 in the regulation of CD8 + CTL exhaustion.…”

mentioning

confidence: 99%

Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Hossain

Liu

Dai

et al. 2020

Medicinal Research Reviews

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“…Forty‐seven percent of the candidates exhibit partial response, and the disease control rate was 97% 114 …”

Section: Clinical Agents Targeting Lag‐3mentioning

confidence: 99%

Advancement of anti‐LAG‐3 in cancer therapy

Li,

Ju,

Miao

et al. 2023

The FASEB Journal

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Immune checkpoint inhibitors have effectively transformed the treatment of many cancers, particularly those highly devastating malignancies. With their widespread popularity, the drawbacks of immune checkpoint inhibitors are also recognized, such as drug resistance and immune‐related systematic side effects. Thus, it never stops investigating novel immune checkpoint inhibitors. Lymphocyte Activation Gene‐3 (LAG‐3) is a well‐established co‐inhibitory receptor that performs negative regulation on immune responses. Recently, a novel FDA‐approved LAG‐3 blocking agent, together with nivolumab as a new combinational immunotherapy for metastatic melanoma, brought LAG‐3 back into focus. Clinical data suggests that anti‐LAG‐3 agents can amplify the therapeutic response of other immune checkpoint inhibitors with manageable side effects. In this review, we elucidate the intercellular and intracellular mechanisms of LAG‐3, clarify the current understanding of LAG‐3 in the tumor microenvironment, identify present LAG‐3‐associated therapeutic agents, discuss current LAG‐3‐involving clinical trials, and eventually address future prospects for LAG‐3 inhibitors.

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“… 41 Subsequently, a phase II trial studied IMP321 and paclitaxel in patients with HR+ MBC (NCT02614833); preliminary data from the run-in phase suggested that IMP321 enhanced antigen-presenting cell (APC) and T-cell activation. 42 There is also interest in understanding if the combination of PD-1 and LAG3 inhibition is synergistic, as in vivo studies demonstrate enhanced benefit with this combination. 43 For example, there is a phase Ib clinical trial studying the safety and efficacy of a PD-1 inhibitor (spartalizumab) and an LAG3 inhibitor (LAG525) in combination with another investigational drug (NIR178, capmatinib, MCS110, or canakinumab) in patients with mTNBC (NCT03742349).…”

Section: Immunotherapymentioning

confidence: 99%

Emerging treatment strategies for metastatic triple-negative breast cancer

2022

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Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is often associated with an aggressive phenotype and a poor prognosis. Cytotoxic chemotherapy remains the mainstay of treatment for most patients with metastatic TNBC (mTNBC), but duration of response is often short and median overall survival is only 12–18 months. Therefore, it is critical to identify novel treatment strategies to improve outcomes for these patients. In this review article, we discuss recent advances in treatment strategies for patients with mTNBC including the use of immune checkpoint inhibitors, targeted therapies, and antibody–drug conjugates. For each topic, we summarize important preclinical and clinical data, discuss implications for clinical practice, and highlight future research directions.

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Combination of paclitaxel and a LAG-3 fusion protein (eftilagimod alpha), as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Final results from the run-in phase of a placebo-controlled randomized phase II.

Cited by 14 publications

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Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Advancement of anti‐LAG‐3 in cancer therapy

Emerging treatment strategies for metastatic triple-negative breast cancer

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Combination of paclitaxel and a LAG-3 fusion protein (eftilagimod alpha), as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Final results from the run-in phase of a placebo-controlled randomized phase II.

Cited by 14 publications

References 0 publications

Reinvigorating exhausted CD8+ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Reinvigorating exhausted CD8+ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Advancement of anti‐LAG‐3 in cancer therapy

Emerging treatment strategies for metastatic triple-negative breast cancer

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Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy