Relatlimab: a novel drug targeting immune checkpoint LAG-3 in melanoma therapy

Relatlimab: a novel drug targeting immune checkpoint LAG-3 in melanoma therapy

10 January 2024 | Jingjing Su, Yiting Fu, Zitong Cui, Zain Abidin, Jingsong Yuan, Xinmiao Zhang, Runmin Li and Chunzhen Zhao
Relatlimab is a human immunoglobulin G4 monoclonal blocking antibody, the first LAG-3 inhibitor and the third immune checkpoint inhibitor with clinical application, following PD-1 and CTLA-4. It binds to the LAG-3 receptor, blocking its interaction with ligands to reduce immunosuppression and promote T-cell proliferation, inducing tumor cell death. On March 18, 2022, the U.S. FDA approved the fixed-dose combination of relatlimab and nivolumab (Opdualag) for the treatment of unresectable or metastatic melanoma in patients aged 12 and older. This study comprehensively describes the mechanism of action and clinical trials of relatlimab and provides an overview of immune checkpoint drugs used in melanoma treatment. Relatlimab targets LAG-3, a key immune checkpoint protein expressed on T-cells. It inhibits LAG-3's interaction with MHC-II, restoring T-cell immune activity and enhancing their ability to kill melanoma cells. The mechanism of action of relatlimab is illustrated in Figure 1. The recommended dose for the fixed-dose combination of relatlimab and nivolumab is 160 mg of relatlimab plus 480 mg of nivolumab for adults weighing more than 40 kg, administered intravenously every 4 weeks. Relatlimab has shown promising results in clinical trials, with a high objective response rate (ORR) and durable response (DOR) in patients with metastatic melanoma. In the RELATIVITY-020 trial, the ORR was 11.5% for the combination therapy of relatlimab and nivolumab. In the RELATIVITY-047 trial, the combination therapy of relatlimab and nivolumab showed a significantly longer progression-free survival (PFS) compared to nivolumab monotherapy. The median PFS for the combination therapy was 10.2 months, compared to 4.6 months for nivolumab monotherapy. The 12-month OS rate for the combination therapy was 77.0%, compared to 71.6% for nivolumab monotherapy. The ORR for the combination therapy was 43.1%, compared to 32.6% for nivolumab monotherapy. Relatlimab and nivolumab combination therapy has shown a better safety profile compared to nivolumab monotherapy, with a lower incidence of treatment-related adverse events (TRAEs). The combination therapy of relatlimab and nivolumab has demonstrated a more significant PFS, lower risk of death, and higher objective response rate compared to nivolumab monotherapy. The combination therapy of relatlimab and nivolumab has also shown manageable safetyRelatlimab is a human immunoglobulin G4 monoclonal blocking antibody, the first LAG-3 inhibitor and the third immune checkpoint inhibitor with clinical application, following PD-1 and CTLA-4. It binds to the LAG-3 receptor, blocking its interaction with ligands to reduce immunosuppression and promote T-cell proliferation, inducing tumor cell death. On March 18, 2022, the U.S. FDA approved the fixed-dose combination of relatlimab and nivolumab (Opdualag) for the treatment of unresectable or metastatic melanoma in patients aged 12 and older. This study comprehensively describes the mechanism of action and clinical trials of relatlimab and provides an overview of immune checkpoint drugs used in melanoma treatment. Relatlimab targets LAG-3, a key immune checkpoint protein expressed on T-cells. It inhibits LAG-3's interaction with MHC-II, restoring T-cell immune activity and enhancing their ability to kill melanoma cells. The mechanism of action of relatlimab is illustrated in Figure 1. The recommended dose for the fixed-dose combination of relatlimab and nivolumab is 160 mg of relatlimab plus 480 mg of nivolumab for adults weighing more than 40 kg, administered intravenously every 4 weeks. Relatlimab has shown promising results in clinical trials, with a high objective response rate (ORR) and durable response (DOR) in patients with metastatic melanoma. In the RELATIVITY-020 trial, the ORR was 11.5% for the combination therapy of relatlimab and nivolumab. In the RELATIVITY-047 trial, the combination therapy of relatlimab and nivolumab showed a significantly longer progression-free survival (PFS) compared to nivolumab monotherapy. The median PFS for the combination therapy was 10.2 months, compared to 4.6 months for nivolumab monotherapy. The 12-month OS rate for the combination therapy was 77.0%, compared to 71.6% for nivolumab monotherapy. The ORR for the combination therapy was 43.1%, compared to 32.6% for nivolumab monotherapy. Relatlimab and nivolumab combination therapy has shown a better safety profile compared to nivolumab monotherapy, with a lower incidence of treatment-related adverse events (TRAEs). The combination therapy of relatlimab and nivolumab has demonstrated a more significant PFS, lower risk of death, and higher objective response rate compared to nivolumab monotherapy. The combination therapy of relatlimab and nivolumab has also shown manageable safety
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