Relatlimab

Relatlimab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetLymphocyte activation gene-3 (LAG-3)
Clinical data
Other namesBMS-986016, relatlimab-rmbw
License data
Routes of
administration		Intravenous
Drug classAntineoplastic
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC6472H9922N1710O2024S38
Molar mass145288.79 g·mol−1

Relatlimab is a monoclonal antibody designed for the treatment of melanoma.[3][4] It is used in combination with nivolumab to treat melanoma.[2][5]

Relatlimab is a Lymphocyte activation gene-3 (LAG-3) inhibitor.[2][5] It is under development by Bristol-Myers Squibb.[2][5] It is made using Chinese hamster ovary cells.[2]

History

In 2004, Drew Pardoll and colleagues discovered that the lymphocyte-activation gene 3, or LAG-3, was a new immune checkpoint.[6][7] Checkpoints inhibitors are proteins that stop the immune system from responding to cancer cells. Checkpoint inhibitor drugs block these proteins, unleashing the immune system to battle the cancer.[8]

As stated in the official John Hopkins Technological Ventures Press:[6]

  • 2004: Drew Pardoll discovers that LAG-3 is a new immune checkpoint.[9]
  • 2010: Pardoll and his research team begin a study to see how relatlimab, a LAG-3 blocking drug, treats cancer in mice.[10]
  • 2012: Findings from the study are published showing that a combination of a LAG-3 blocker and PD-1 blocker is an effective cancer treatment.[8]
  • 2016: The Join effort including Drew Pardoll, Shirley Liu, Cliff Meyer and Eduardo Gusmao has led to significant advances on the effectiveness as LAG-3 + PD-1 checkpoint blockade immunotherapy.[11]
  • 2018: The RELATIVITY-047 trial begins enrolling patients and randomly assigning them to receive relatlimab with nivolumab or nivolumab alone.[12]
  • January 2022: Results from the RELATIVITY-047 trial published in The New England Journal of Medicine show the combination treatment with relatlimab to be a more effective treatment than nivolumab alone.[13]
  • March 2022: The FDA gives approval for the combination treatment (relatlimab and nivolumab, marketed as Opdualag) as a new therapy for patients with metastatic or inoperable melanoma.[14]

The combination nivolumab/relatlimab (Opdualag) was approved for medical use in the United States in March 2022.[2][5]

Names

Relatlimab is the United States Adopted Name (USAN) and the international nonproprietary name (INN).[15][16][17]

References

  1. ^ "Notice: Multiple additions to the Prescription Drug List (PDL) [2023-12-22]". Health Canada. 22 December 2023. Retrieved 3 January 2024.
  2. ^ a b c d e f "Opdualag- nivolumab and relatlimab-rmbw injection". DailyMed. 18 March 2022. Retrieved 22 March 2022.
  3. ^ Cavagnaro JA, Cosenza ME, eds. (2021). Translational Medicine: Optimizing Preclinical Safety Evaluation of Biopharmaceuticals. Boca Raton, Florida: CRC Press. ISBN 978-1-00-047185-4.
  4. ^ Robert C (December 2021). "LAG-3 and PD-1 blockade raises the bar for melanoma". Nature Cancer. 2 (12): 1251–3. doi:10.1038/s43018-021-00276-8. PMID 35121906. S2CID 245407697.
  5. ^ a b c d "U.S. Food and Drug Administration Approves First LAG-3-Blocking Antibody Combination, Opdualag (nivolumab and relatlimab-rmbw), as Treatment for Patients with Unresectable or Metastatic Melanoma" (Press release). Bristol Myers Squibb. 18 March 2022. Retrieved 19 March 2022 – via Business Wire.
  6. ^ a b Johns Hopkins Technology Ventures (December 2024). "10 Innovations in 10 Years: Relatlimab". John Hopkins Technological Ventures. Retrieved 23 January 2026.
  7. ^ Ruffo E, Wu RC, Bruno TC, Workman CJ, Vignali DA (April 2019). "Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor". Seminars in Immunology. 42 101305. doi:10.1016/j.smim.2019.101305. PMC 6920665. PMID 31604537.
  8. ^ a b Pardoll DM (March 2012). "The blockade of immune checkpoints in cancer immunotherapy". Nature Reviews. Cancer. 12 (4): 252–264. doi:10.1038/nrc3239. PMC 4856023. PMID 22437870.
  9. ^ Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA (October 2004). "Role of LAG-3 in regulatory T cells". Immunity. 21 (4): 503–513. doi:10.1016/j.immuni.2004.08.010. PMID 15485628.
  10. ^ Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL (2010). "Phase I study of single-agent anti–programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates". Journal of Clinical Oncology. 28 (19): 3167–3175. doi:10.1200/JCO.2009.26.7609. PMC 4834717. PMID 20516446.
  11. ^ Gusmao EG, Allhoff M, Zenke M, Costa IG (April 2016). "Analysis of computational footprinting methods for DNase sequencing experiments". Nature Methods. 13 (4): 303–309. doi:10.1038/nmeth.3772. PMID 26901649.
  12. ^ Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM (2018). "Neoadjuvant PD-1 blockade in resectable lung cancer". New England Journal of Medicine. 378 (21): 1976–1986. doi:10.1056/NEJMoa1716078. PMC 6223617. PMID 29658848.
  13. ^ Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutiérrez E, Rutkowski P, Gogas HJ, Lao CD, Janoski de Menezes J, Dalle S, Arance A, Grob JJ, Srivastava S, Abaskharoun M, Hamilton M, Keidel S, Simonsen KL, Sobiesk AM, Li B, Hodi FS, Long GV (2022). "Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma". New England Journal of Medicine. 386 (1): 24–34. doi:10.1056/NEJMoa2109970. PMC 9844513. PMID 34986285.
  14. ^ Paik J (May 2022). "Nivolumab plus relatlimab: first approval". Drugs. 82 (8): 925–931. doi:10.1007/s40265-022-01723-1. PMID 35543970.
  15. ^ "Relatlimab". American Medical Association. Retrieved 22 March 2022.
  16. ^ Statement On A Nonproprietary Name Adopted By The USAN Council - Relatlimab Archived 2018-09-24 at the Wayback Machine, American Medical Association.
  17. ^ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 81". WHO Drug Information. 33 (1). 2019. hdl:10665/330896.
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