NEJM: The third-generation immune checkpoint comes into play: LAG-3+PD-1, doubles progression-free survival in advanced cancer

With the development of biology and medicine, human beings have a deeper understanding of cancer and their own immune system, and human beings have made major breakthroughs in the field of cancer treatment, especially the immune checkpoints represented by PD-1/PD-L1.
The discovery and the emergence of cancer immunotherapy represented by immune checkpoint inhibitors can be said to have completely changed the pattern of cancer treatment and brought hope to cancer patients
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Both LAG-3 (lymphocyte activation gene 3) and PD-1 (programmed death receptor 1) are inhibitory immune checkpoints on T cells that lead to T cell exhaustion
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Recently, Professor Hussein Tawbi of the University of Texas MD Anderson Cancer Center and dozens of medical institutions around the world published a clinical trial paper entitled: Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma in the New England Journal of Medicine ( NEJM ) .

In this phase II/III double-blind randomized controlled clinical trial, a total of 714 patients with advanced melanoma participated, the experimental group received Relatlimab + Nivolumab combination therapy, and the control group received Nivolumab monotherapy
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Nivolumab (anti-PD-1 monoclonal antibody) was developed by Bristol-Myers Squibb Company (BMS) and has been approved for the treatment of various cancers such as melanoma and non-small cell lung cancer.
It is also one of the best-selling monoclonal antibody drugs in the world.
one
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Relatlimab (anti-LAG-3 monoclonal antibody) was also developed by BMS.
LAG-3 is a molecule expressed on the surface of effector T cells and regulatory T cells, which can regulate the response, activation and proliferation of T cells
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In this phase II/III double-blind randomized controlled clinical trial, a total of 714 patients with previously untreated advanced melanoma were randomized 1:1 to receive either Relatlimab + Nivolumab combination therapy or Nivolumab monotherapy
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Results of the trial showed that median progression-free survival was 10.
1 months in the combination arm and 4.
6 months in the monotherapy arm
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These are the results of the first Phase II/III clinical trial of a third-generation immune checkpoint (LAG-3) inhibitor after CTLA-4 and PD-1/PD-L1, and the first to compare immune checks A clinical trial of the efficacy of point inhibitor combination therapy versus nivolumab monotherapy in melanoma
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The research team said that the combination of Relatlimab + Nivolumab had a clear benefit compared to Nivolumab monotherapy , doubling progression-free survival and reducing the risk of disease progression or death by 25%
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Over the past decade, we have seen the historic development of immune checkpoint inhibitors, with PD-1 inhibitors and CTLA-4 inhibitors both monotherapy and combination therapy approved as first-line treatment options for metastatic melanoma
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Original source:

Hussein A.