Sacituzumab govitecan

Sacituzumab govitecan is indicated for the treatment of adults with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease; people with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease; and for people with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor.{{cite web | title=FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer | website=U.S. Food and Drug Administration (FDA) | date=13 April 2021 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer | access-date=13 April 2021 | archive-date=13 April 2021 | archive-url=https://web.archive.org/web/20210413184403/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer | url-status=live }} {{PD-notice}}

It is also indicated for the treatment of people with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.

Sacituzumab govitecan is a conjugate of the humanized anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan.{{cite journal | vauthors = Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Arrojo R, Liu D, Rossi EA, Chang CH, Goldenberg DM | display-authors = 6 | title = Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers | journal = Bioconjugate Chemistry | volume = 26 | issue = 5 | pages = 919–931 | date = May 2015 | pmid = 25915780 | doi = 10.1021/acs.bioconjchem.5b00223 }} Each antibody having on average 7.6 molecules of SN-38 attached.{{cite web|url=https://www.medpagetoday.com/reading-room/asco/breast-cancer/58805|title=Novel Agents are Targeting Drivers of TNBC|date=28 June 2016|website=www.medpagetoday.com|access-date=12 June 2019|archive-date=13 June 2021|archive-url=https://web.archive.org/web/20210613054725/https://www.medpagetoday.com/reading-room/asco/breast-cancer/58805|url-status=live}} Linkage to an antibody allows the drug to specifically target cells expressing Trop-2.

Sacituzumab govitecan is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate, meaning that the drug targets the Trop-2 receptor that helps the cancer grow, divide and spread, and is linked to topoisomerase inhibitor, which is a chemical compound that is toxic to cancer cells. Approximately two of every ten breast cancer diagnoses worldwide are triple-negative. Triple-negative breast cancer is a type of breast cancer that tests negative for estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2) protein. Therefore, triple-negative breast cancer does not respond to hormonal therapy medicines or medicines that target HER2.

Immunomedics announced in 2013, that it had received fast track designation from the US Food and Drug Administration (FDA) for the compound as a potential treatment for non-small cell lung cancer, small cell lung cancer, and metastatic triple-negative breast cancer. Orphan drug status was granted for small cell lung cancer and pancreatic cancer.{{cite web | title=Sacituzumab govitecan Orphan Drug Designation and Approval | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=433514 | access-date=22 April 2020 | archive-date=24 June 2021 | archive-url=https://web.archive.org/web/20210624194946/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=433514 | url-status=live }}{{cite web | title=Sacituzumab govitecan Orphan Drug Designation and Approval | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=415413 | access-date=22 April 2020 | archive-date=2 July 2020 | archive-url=https://web.archive.org/web/20200702071110/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=415413 | url-status=live }} In February 2016, Immunomedics announced that sacituzumab govitecan had received an FDA breakthrough therapy designation (a classification designed to expedite the development and review of drugs that are intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition) for the treatment of people with triple-negative breast cancer who have failed at least two other prior therapies for metastatic disease.{{cite web|url=https://www.curetoday.com/articles/new-therapy-shows-early-promise-continues-to-progress-in-triple-negative-breast-cancer|title=New Therapy Shows Early Promise, Continues to Progress in Triple-Negative Breast Cancer|website=Cure Today|date=8 February 2016 |access-date=12 June 2019|archive-date=22 December 2019|archive-url=https://web.archive.org/web/20191222102840/https://www.curetoday.com/articles/new-therapy-shows-early-promise-continues-to-progress-in-triple-negative-breast-cancer|url-status=live}}{{cite press release | title=U.S. Food and Drug Administration (FDA) Grants Breakthrough Therapy Designation to Immunomedics for Sacituzumab Govitecan for the Treatment of Patients With Triple-Negative Breast Cancer | via=GlobeNewswire | publisher=Immunomedics | date=5 February 2016 | url=http://www.globenewswire.com/news-release/2016/02/05/808211/0/en/U-S-Food-and-Drug-Administration-FDA-Grants-Breakthrough-Therapy-Designation-to-Immunomedics-for-Sacituzumab-Govitecan-for-the-Treatment-of-Patients-With-Triple-Negative-Breast-Can.html | access-date=25 April 2020 | archive-date=25 April 2020 | archive-url=https://web.archive.org/web/20200425201355/https://www.globenewswire.com/news-release/2016/02/05/808211/0/en/U-S-Food-and-Drug-Administration-FDA-Grants-Breakthrough-Therapy-Designation-to-Immunomedics-for-Sacituzumab-Govitecan-for-the-Treatment-of-Patients-With-Triple-Negative-Breast-Can.html | url-status=live }}

Sacituzumab govitecan was added to the proposed International nonproprietary name (INN) list in 2015,{{cite journal | vauthors=((World Health Organization)) | year=2015 | title=International nonproprietary names for pharmaceutical substances (INN): proposed INN: list 113 | journal=WHO Drug Information | volume=29 | issue=2 | pages=260–1 |hdl=10665/331080 | hdl-access=free }} and to the recommended list in 2016.{{cite journal | vauthors=((World Health Organization)) | year=2016 | title=International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 75 | journal=WHO Drug Information | volume=30 | issue=1 | pages=151–3 |hdl=10665/331046 | hdl-access=free }}

Sacituzumab govitecan-hziy was approved for medical use in the United States in April 2020.{{cite web | title=Drug Trial Snapshot: Trodelvy | website=U.S. Food and Drug Administration (FDA) | date=22 April 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-trodelvy | access-date=29 April 2020 | archive-date=30 April 2020 | archive-url=https://web.archive.org/web/20200430051920/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-trodelvy | url-status=live }} {{PD-notice}}{{cite web | title=Trodelvy: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761115 | access-date=22 April 2020 | archive-date=28 July 2020 | archive-url=https://web.archive.org/web/20200728043557/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761115 | url-status=live }}{{cite web | title=FDA grants accelerated approval to sacituzumab govitecan-hziy for metastatic triple negative breast cancer | website=U.S. Food and Drug Administration (FDA) | date=22 April 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-sacituzumab-govitecan-hziy-metastatic-triple-negative-breast-cancer | access-date=23 April 2020 | archive-date=23 April 2020 | archive-url=https://web.archive.org/web/20200423182328/https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-sacituzumab-govitecan-hziy-metastatic-triple-negative-breast-cancer | url-status=live }} {{PD-notice}}

Sacituzumab govitecan-hziy was approved based on the results of IMMU-132-01, a multicenter, single-arm clinical trial (NCT01631552) of 108 participants with metastatic triple-negative breast cancer who had received at least two prior treatments for metastatic disease. Of the 108 participants involved within the study, 107 were female and 1 was male.{{cite journal | vauthors = Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K | display-authors = 6 | title = Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer | journal = The New England Journal of Medicine | volume = 380 | issue = 8 | pages = 741–751 | date = February 2019 | pmid = 30786188 | doi = 10.1056/NEJMoa1814213 | s2cid = 73489970 | doi-access =free }} Participants received sacituzumab govitecan-hziy at a dose of 10{{nbsp}}milligrams per kilogram of body weight intravenously on days one and eight every 21 days. Treatment with sacituzumab govitecan-hziy was continued until disease progression or unacceptable toxicity. Tumor imaging was obtained every eight weeks. The efficacy of sacituzumab govitecan-hziy was based on the overall response rate (ORR) – which reflects the percentage of participants that had a certain amount of tumor shrinkage. The ORR was 33.3% (95% confidence interval [CI], 24.6 to 43.1). Additionally, with the 33.3% of study participants who achieved a response, 2.8% of participants experienced complete responses. The median time to response in participants was 2.0 months (range, 1.6 to 13.5), the median duration of response was 7.7 months (95% confidence interval [CI], 4.9 to 10.8), the median progression free survival was 5.5 months, and the median overall survival was 13.0 months. Of the participants that achieved an objective response to sacituzumab govitecan-hziy, 55.6% maintained their response for six or more months and 16.7% maintained their response for twelve or more months.

Sacituzumab govitecan-hziy was granted accelerated approval along with priority review, breakthrough therapy, and fast track designations. The U.S. Food and Drug Administration (FDA) granted approval of Trodelvy to Immunomedics, Inc.

In April 2021, the FDA granted regular approval to sacituzumab govitecan for people with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.{{cite web | title=FDA grants regular approval to sacituzumab govitecan for TNBC | website=U.S. Food and Drug Administration (FDA) | date=8 April 2021 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer | access-date=9 April 2021 | archive-date=8 April 2021 | archive-url=https://web.archive.org/web/20210408125425/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer | url-status=live }} {{PD-notice}} Efficacy and safety were evaluated in a multicenter, open-label, randomized trial (ASCENT; NCT02574455) conducted in 529 participants with unresectable locally advanced or mTNBC who had relapsed after at least two prior chemotherapies, one of which could be in the neoadjuvant or adjuvant setting, if progression occurred within twelve months. Participants were randomized (1:1) to receive sacituzumab govitecan, 10{{nbsp}}mg/kg as an intravenous infusion, on days 1 and 8 of a 21-day (n=267) cycle or physician's choice of single agent chemotherapy (n=262).

In April 2021, the FDA granted accelerated approval to sacituzumab govitecan for people with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor. Efficacy and safety were evaluated in TROPHY (IMMU-132-06; NCT03547973), a single-arm, multicenter trial that enrolled 112 participants with locally advanced or mUC who received prior treatment with a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor.

In February 2023, the FDA approved sacituzumab govitecan for people with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.{{cite web |date=3 February 2023 |title=FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-hr-positive-breast-cancer |publisher=FDA |access-date=9 February 2023 |archive-date=9 February 2023 |archive-url=https://web.archive.org/web/20230209085057/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-hr-positive-breast-cancer |url-status=live }} {{PD-notice}}{{Cite web |title=FDA Approves Trodelvy for HER2-Negative, HR-Positive Metastatic Breast Cancer |url=https://www.curetoday.com/view/fda-approves-trodelvy-for-her2-negative-hr-positive-metastatic-breast-cancer |access-date=9 February 2023 |website=Cure Today |date=3 February 2023 |archive-date=9 February 2023 |archive-url=https://web.archive.org/web/20230209085057/https://www.curetoday.com/view/fda-approves-trodelvy-for-her2-negative-hr-positive-metastatic-breast-cancer |url-status=live }}{{Cite press release |title=U.S. FDA Approves Trodelvy in Pre-treated HR+/HER2- Metastatic Breast Cancer |url=https://www.gilead.com/news-and-press/press-room/press-releases/2023/2/us-fda-approves-trodelvy-in-pretreated-hrher2-metastatic-breast-cancer |access-date=9 February 2023 |website=Gilead |archive-date=9 February 2023 |archive-url=https://web.archive.org/web/20230209085058/https://www.gilead.com/news-and-press/press-room/press-releases/2023/2/us-fda-approves-trodelvy-in-pretreated-hrher2-metastatic-breast-cancer |url-status=live }}

On 14 October 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Trodelvy, intended for the treatment of unresectable or metastatic triple-negative breast cancer.{{cite web | title=Trodelvy: Pending EC decision | website=European Medicines Agency | date=15 October 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/trodelvy | access-date=15 October 2021 | archive-date=18 October 2021 | archive-url=https://web.archive.org/web/20211018120519/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/trodelvy | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The applicant for this medicinal product is Gilead Sciences Ireland UC. Sacituzumab govitecan was approved for medical use in the European Union in November 2021.{{cite web | title=Trodelvy Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1592.htm | access-date=3 March 2023}}

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• {{cite journal | vauthors = Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K | display-authors = 6 | title = Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer | journal = The New England Journal of Medicine | volume = 380 | issue = 8 | pages = 741–751 | date = February 2019 | pmid = 30786188 | doi = 10.1056/NEJMoa1814213 | s2cid = 73489970 | doi-access =free }}
• {{cite journal | vauthors = Weiss J, Glode A, Messersmith WA, Diamond J | title = Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer | journal = Expert Review of Anticancer Therapy | volume = 19 | issue = 8 | pages = 673–679 | date = August 2019 | pmid = 31398063 | doi = 10.1080/14737140.2019.1654378 | s2cid = 199518147 }}

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• {{cite journal | title=Sacituzumab govitecan | journal=ADC Review | url=https://www.adcreview.com/drugmap/immu-132-hrs7-sn38/ }}
• {{cite web | title=Sacituzumab govitecan | website=National Cancer Institute | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/sacituzumab-govitecan }}
• {{ClinicalTrialsGov|NCT01631552|Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers}}
• {{ClinicalTrialsGov|NCT02574455|ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT)}}
• {{ClinicalTrialsGov|NCT03547973|Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer}}
• {{MeshName|Sacituzumab govitecan}}

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Category:Antibody-drug conjugates

Category:Cancer treatments

Category:Monoclonal antibodies for tumors

Category:Orphan drugs