Talquetamab

{{Short description|Monoclonal antibody}} {{Use American English|date=October 2023}} {{Use dmy dates|date=June 2024}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | type = mab | image = | alt = | caption =

| mab_type = BiTE | source = zu | target = GPRC5D, CD3

| pronounce = | tradename = Talvey | Drugs.com = {{drugs.com|monograph|talquetamab}} | MedlinePlus = a623047 | DailyMedID = Talquetamab | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category= Contraindicated<ref name="Talvey FDA label" /> | routes_of_administration = Subcutaneous | ATC_prefix = L01 | ATC_suffix = FX29

| legal_AU = S4 | legal_AU_comment = <ref>{{cite web | title=Talvey (Janssen-Cilag Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=9 December 2024 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/talvey-janssen-cilag-pty-ltd | access-date=19 December 2024}}</ref><ref>{{cite web | title=Talvey talquetamab 2 mg/mL solution for injection vial (409913) | website=Therapeutic Goods Administration (TGA) | date=27 September 2024 | url=https://www.tga.gov.au/resources/artg/409913 | access-date=19 December 2024}}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = /{{nbsp}}Schedule D<ref>{{cite web | title=Talvey Product information | website=Health Canada | date=30 April 2024 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=103601 | access-date=21 June 2024}}</ref><ref>{{cite web | title=Talvey Product information | website=Health Canada | date=30 April 2024 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=103601 | access-date=15 July 2024}}</ref><ref>{{cite web | title=Summary Basis of Decision for Talvey | website=Drug and Health Products Portal | date=1 September 2012 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1732553847408 | access-date=17 December 2024}}</ref><ref>{{cite web | title=Talvey product information | website=Health Canada | date=30 April 2024 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=103601 | access-date=27 December 2024}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Talvey FDA label" /> | legal_EU = Rx-only | legal_EU_comment = <ref name="Talvey EPAR" /><ref name="EU Talvey PI" /> | legal_UN =  | legal_UN_comment = | legal_status =

| CAS_number = 2226212-40-2 | CAS_supplemental = | PubChem = | IUPHAR_ligand = | DrugBank = DB16678 | ChemSpiderID = | UNII = 4W3KFI3TN3 | KEGG = D12180 | ChEBI = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = | synonyms = Talquetamab-tgvs }}

'''Talquetamab''', sold under the brand name '''Talvey''', is a humanized monoclonal antibody used for the treatment of multiple myeloma.<ref name="Talvey FDA label">{{cite web | title=Talvey- talquetamab injection | work = DailyMed | publisher = U.S. National Library of Medicine | date=18 August 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9001355e-003d-4d4e-b4ce-337e0fd14952 | access-date=23 August 2023 | archive-date=24 August 2023 | archive-url=https://web.archive.org/web/20230824183008/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9001355e-003d-4d4e-b4ce-337e0fd14952 | url-status=live }}</ref><ref name="Talvey EPAR">{{cite web | title=Talvey EPAR | website=European Medicines Agency | date=21 September 2023 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/talvey | access-date=6 October 2023}}</ref> It is a bispecific GPRC5D-directed CD3 T-cell engager.<ref name="Talvey FDA label" /> Talquetamab is a bispecific antibody against two targets: human CD3, a T-cell surface antigen, and human G-protein coupled receptor family C group 5 member D (GPRC5D), a tumor-associated antigen with potential antineoplastic activity.<ref name=NCI>{{cite web | url = https://www.cancer.gov/publications/dictionaries/cancer-drug/def/talquetamab | title = Talquetamab | work = NCI Drug Dictionary | publisher = National Cancer Institute | access-date = 30 January 2023 | archive-date = 11 August 2023 | archive-url = https://web.archive.org/web/20230811074023/https://www.cancer.gov/publications/dictionaries/cancer-drug/def/talquetamab | url-status = live }}</ref> Talquetamab binds both targets, drawing the T cells close to the tumor cells, causing a cytotoxic T-lymphocyte response.<ref name=NCI/> It is being developed by Janssen Pharmaceuticals.<ref>{{cite journal | vauthors = Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NW, Rodríguez-Otero P, Askari E, Mateos MV, Costa LJ, Caers J, Verona R, Girgis S, Yang S, Goldsmith RB, Yao X, Pillarisetti K, Hilder BW, Russell J, Goldberg JD, Krishnan A | title = Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma | journal = The New England Journal of Medicine | volume = 387 | issue = 24 | pages = 2232–2244 | date = December 2022 | pmid = 36507686 | doi = 10.1056/NEJMoa2204591 | s2cid = 254560960 | doi-access = free }}</ref>

The most common adverse reactions include cytokine release syndrome, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.<ref name="FDA talquetamab" />

Talquetamab was approved for medical use in both the United States<ref name="Talvey FDA label" /><ref name="FDA talquetamab">{{cite web | title=FDA grants accelerated approval to talquetamab-tgvs for relapsed or refractory multiple myeloma | website=U.S. Food and Drug Administration (FDA) | date=9 August 2023 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-talquetamab-tgvs-relapsed-or-refractory-multiple-myeloma | access-date=10 August 2023 | archive-date=11 August 2023 | archive-url=https://web.archive.org/web/20230811072719/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-talquetamab-tgvs-relapsed-or-refractory-multiple-myeloma | url-status=dead }} {{PD-notice}}</ref><ref name="FDA approval letter">{{cite web | vauthors = Theoret MR | date = 2023 | title = Talvey (talquetamab-tgvs) injection | work = Approval Letter | publisher = U.S. Food and Drug Administration | url = https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761342Orig1s000ltr.pdf | archive-url = https://web.archive.org/web/20230811072810/https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/761342Orig1s000ltr.pdf | archive-date=11 August 2023 }} {{PD-notice}}</ref> and the European Union<ref name="EU Talvey PI">{{cite web | title=Talvey Product information | website=Union Register of medicinal products | date=22 August 2023 | url=https://ec.europa.eu/health/documents/community-register/html/h1748.htm | access-date=25 August 2023 | archive-date=25 August 2023 | archive-url=https://web.archive.org/web/20230825211406/https://ec.europa.eu/health/documents/community-register/html/h1748.htm | url-status=live }}</ref> in August 2023. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.<ref>{{cite report | title=New Drug Therapy Approvals 2023 | website=U.S. Food and Drug Administration (FDA) | date=January 2024 | url=https://www.fda.gov/media/175253/download | format=PDF | access-date=9 January 2024 | archive-url=https://web.archive.org/web/20240110032419/https://www.fda.gov/media/175253/download | archive-date=10 January 2024 | url-status=dead }}</ref> == Medical uses == Talquetamab is indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.<ref name="Talvey FDA label" /><ref name="FDA talquetamab" /><ref name="EU Talvey PI"/><ref name="Talvey EPAR" />

== Adverse effects == The US Food and Drug Administration (FDA) label prescribing information has a boxed warning for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity.<ref name="Talvey FDA label" /><ref name="FDA talquetamab" />

== Structure == In 2024, the molecular structure of GPRC5D complexed with talquetamab Fab (anti GPRC5D) were characterized by using cryogenic electron microscopy. Structural analysis of the complex has revealed that talquetamab Fab lodges at a shallow pocket on the extracellular surface of GPRC5D and recognizes ECLs and TM3/5/7 of one GPRC5D protomer via six CDRs.<ref>{{Cite journal |vauthors=Jeong J, Park J, Young Mo G, Shin J, Cho Y |year=2024 |title=Structural Basis for the Recognition of GPRC5D by Talquetamab, a Bispecific Antibody for Multiple Myeloma |url=https://doi.org/10.1016/j.jmb.2024.168748 |journal=Journal of Molecular Biology |volume=436 |issue=20 |doi=10.1016/j.jmb.2024.168748 |issn=0022-2836 |pmid=39181182|url-access=subscription }}</ref>

== History == Efficacy was evaluated in MMY1001 (MonumenTAL-1) (NCT03399799, NCT04634552), a single-arm, open-label, multicenter study that included 187 participants who had previously received at least four prior systemic therapies.<ref name="FDA talquetamab" /> Participants received talquetamab-tgvs 0.4 mg/kg subcutaneously weekly, following two step-up doses in the first week of therapy, or talquetamab-tgvs 0.8 mg/kg subcutaneously biweekly (every two weeks), following three step-up doses, until disease progression or unacceptable toxicity.<ref name="FDA talquetamab" />

The main efficacy outcome measures were overall response rate and duration of response as assessed by an independent review committee using IMWG criteria.<ref name="FDA talquetamab" /> The primary efficacy population consisted of participants who had previously received at least four prior lines of therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.<ref name="FDA talquetamab" /> Overall response rate in the 100 participants receiving 0.4 mg/kg weekly was 73% (95% confidence interval (CI): 63.2%, 81.4%) and median duration of response was 9.5 months (95% CI: 6.5, not estimable).<ref name="FDA talquetamab" /> Overall response rate in the 87 participants receiving 0.8 mg/kg biweekly was 73.6% (95% CI: 63%, 82.4%) and median duration of response was not estimable.<ref name="FDA talquetamab" /> An estimated 85% of responders maintained response for at least nine months.<ref name="FDA talquetamab" />

The FDA granted the application for talquetamab priority review, breakthrough therapy, and orphan drug designations.<ref name="FDA talquetamab" />

== Society and culture == === Legal status === In the United States, Janssen received breakthrough therapy designation for talquetamab in June 2022, for the treatment of adults with relapsed or refractory multiple myeloma, who have previously received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.<ref>{{cite web | url = https://www.targetedonc.com/view/fda-grants-breakthrough-therapy-designation-to-talquetamab-for-r-r-myeloma | title = FDA Grants Breakthrough Therapy Designation to Talquetamab for R/R Myeloma | publisher = Targeted Oncology | date = 29 June 2022 | access-date = 30 January 2023 | archive-date = 11 August 2023 | archive-url = https://web.archive.org/web/20230811074545/https://www.targetedonc.com/view/fda-grants-breakthrough-therapy-designation-to-talquetamab-for-r-r-myeloma | url-status = live }}</ref> Janssen filed for approval from the FDA in December 2022,<ref>{{cite press release | url = https://www.prnewswire.com/news-releases/janssen-submits-biologics-license-application-to-us-fda-for-talquetamab-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma-301699241.html | title = Janssen Submits Biologics License Application to U.S. FDA for Talquetamab for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma | work = The Janssen Pharmaceutical Companies of Johnson & Johnson | date = 9 December 2022 }}</ref> and from the European Medicines Agency in January 2023.<ref>{{cite press release | url = https://www.globenewswire.com/news-release/2023/01/03/2581869/0/en/Janssen-Submits-Marketing-Authorisation-Application-to-the-European-Medicines-Agency-Seeking-Approval-of-Talquetamab-for-the-Treatment-of-Patients-with-Relapsed-or-Refractory-Multi.html | title = Application to the European Medicines Agency Seeking Approval of Talquetamab for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma | date = 3 January 2023 | work = Janssen Pharmaceutica NV }}</ref>

On 20 July 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Talvey, intended for the treatment of multiple myeloma.<ref name="Talvey: Pending EC decision" /> Talvey was reviewed under EMA's accelerated assessment program.<ref name="Talvey: Pending EC decision" /> The applicant for this medicinal product is Janssen-Cilag International N.V.<ref name="Talvey: Pending EC decision">{{cite web | title=Talvey: Pending EC decision | website=European Medicines Agency (EMA) | date=21 July 2023 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/talvey | access-date=25 August 2023 | archive-date=25 August 2023 | archive-url=https://web.archive.org/web/20230825210919/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/talvey | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Talquetamab was approved for medical use in the European Union in August 2023.<ref name="EU Talvey PI" /><ref name="Talvey EPAR" />

== References == {{reflist}}

== External list == * {{ClinicalTrialsGov|NCT03399799|Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1)}} * {{ClinicalTrialsGov|NCT04634552|A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma}}

Category:Monoclonal antibodies for tumors Category:Orphan drugs