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
.

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
.

Previous studies have demonstrated that Relatlimab (anti-LAG-3 monoclonal antibody) + Nivolumab (anti-PD-1 monoclonal antibody) combination therapy is safe and effective in patients with previously treated melanoma, but not in previously untreated melanoma Patient safety and therapeutic activity remain to be investigated

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 ) .

NEJM NEJM Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma

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
.

The results of the clinical trial showed that compared with the control group, the median progression-free survival of the experimental group was doubled (10.
1 months vs 4.

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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Melanoma Melanoma Non-Small Cell Lung Cancer Non-Small Cell Lung Cancer

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
.

Preclinical studies have shown that blocking LAG-3 prevents T cell exhaustion and promotes T cell antitumor immune responses

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
.

The combination therapy group was administered a dose of 160 mg of Relatlimab and a dose of 480 mg of Nivolumab; the monotherapy group was administered a dose of 480 mg of Nivolumab

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
.

After 12 months of follow-up, progression-free survival was 47.

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%
.

Relatlimab Relatlimab Nivolumab Nivolumab

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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Combination therapy of PD-1 and CTLA-4 benefited patients more than monotherapy, but also greatly affected quality of life, with a serious adverse event rate of more than 50%

Original source:

Hussein A.

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