Sacituzumab govitecan

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Sacituzumab govitecan
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetTrop-2
Names
Trade namesTrodelvy
Other namesIMMU-132, hRS7-SN-38, sacituzumab govitecan-hziy
Clinical data
Main usesTriple-negative breast cancer, urothelial cancer[1]
Side effectsNausea, low neutrophils, diarrhea, tiredness, low red blood cells, hair loss[2]
Pregnancy
category
  • Contraindicated
Routes of
use
Intravenous
External links
AHFS/Drugs.comMonograph
US NLMSacituzumab govitecan
MedlinePlusa620034
Legal
License data
Legal status
Chemical and physical data
FormulaC76H104N12O24S
Molar mass1601.79 g·mol−1
3D model (JSmol)
  • CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)C4(CC)OC(=O)OCC5=CC=C(C=C5)NC(=O)C(CCCCN)NC(=O)COCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCN6C=C(N=N6)CNC(=O)C7CCC(CC7)CN8C(=O)CC(C8=O)SCC(C(=O)O)N)C2=NC9=C1C=C(C=C9)O
  • InChI=1S/C76H104N12O24S/c1-3-55-56-37-54(89)16-17-61(56)83-68-57(55)43-87-63(68)38-59-58(71(87)95)45-110-74(99)76(59,4-2)112-75(100)111-44-50-10-14-52(15-11-50)81-70(94)62(7-5-6-18-77)82-66(91)47-109-46-65(90)79-19-21-101-23-25-103-27-29-105-31-33-107-35-36-108-34-32-106-30-28-104-26-24-102-22-20-86-42-53(84-85-86)40-80-69(93)51-12-8-49(9-13-51)41-88-67(92)39-64(72(88)96)113-48-60(78)73(97)98/h10-11,14-17,37-38,42,49,51,60,62,64,89H,3-9,12-13,18-36,39-41,43-48,77-78H2,1-2H3,(H,79,90)(H,80,93)(H,81,94)(H,82,91)(H,97,98)/t49?,51?,60-,62-,64?,76-/m0/s1
  • Key:ULRUOUDIQPERIJ-PQURJYPBSA-N

Sacituzumab govitecan, sold under the brand name Trodelvy, is a medication used to treat triple-negative breast cancer and urothelial cancer.[3][1] Specifically it is used in cases were the cancer has spread and other treatments have failed.[2] It is given by injection into a vein.[4]

Common side effects include nausea, low neutrophils, diarrhea, tiredness, low red blood cells, vomiting, hair loss, constipation, decreased appetite, rash and abdominal pain.[2] Other side effects may include infertility and anaphylaxis.[2] Use in pregnancy or breastfeeding may harm the baby baby.[5] It is a TROP-2-directed antibody joined to a topoisomerase inhibitor.[2][4]

Sacituzumab govitecan was approved for medical use in the United States in 2020.[2] As of 2021 it is not available in Europe due to a lack of supply.[6] It costs about 310,500 USD per year as of 2021 for a 70 kg person.[7]

Medical uses

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;[8] 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;[9] 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.[10]

Dosage

It is generally used at a dose of 10 mg/kg every 1st and 8th day in a three week period.[2]

Mechanism

Sacituzumab govitecan is a conjugate of the humanized anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan.[11] Each antibody having on average 7.6 molecules of SN-38 attached.[12] SN-38 is too toxic to administer directly to patients, but linkage to an antibody allows the drug to specifically target cells containing Trop-2.[medical citation needed]

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.[3] Approximately two of every ten breast cancer diagnoses worldwide are triple-negative.[3] 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.[3] Therefore, triple-negative breast cancer does not respond to hormonal therapy medicines or medicines that target HER2.[3]

History

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.[13][14] 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.[15][16]

Sacituzumab govitecan was added to the proposed INN list in 2015,[17] and to the recommended list in 2016.[18]

Sacituzumab govitecan-hziy was approved for medical use in the United States in April 2020.[3][19][9][20][8]

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.[3][8][19] Of the 108 participants involved within the study, 107 were female and 1 was male.[21] Participants received sacituzumab govitecan-hziy at a dose of 10 milligrams per kilogram of body weight intravenously on days one and eight every 21 days.[8][21] Treatment with sacituzumab govitecan-hziy was continued until disease progression or unacceptable toxicity.[21] Tumor imaging was obtained every eight weeks.[8][19] 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.[3][8] The ORR was 33.3% (95% confidence interval [CI], 24.6 to 43.1). [3][8][21] Additionally, with the 33.3% of study participants who achieved a response, 2.8% of participants experienced complete responses.[21] 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.[21] 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.[3][8]

Sacituzumab govitecan-hziy was granted accelerated approval along with priority review, breakthrough therapy, and fast track designations.[3][8][9] The U.S. Food and Drug Administration (FDA) granted approval of Trodelvy to Immunomedics, Inc.[3]

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.[9] 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.[9] Participants were randomized (1:1) to receive sacituzumab govitecan, 10 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).[9]

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.[10] 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.[10]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[22]

References

  1. 1.0 1.1 1.2 "Trodelvy- sacituzumab govitecan powder, for solution". DailyMed. Retrieved 9 April 2021.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Sacituzumab Govitecan-hziy Monograph for Professionals". Drugs.com. Retrieved 9 October 2021.
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 "FDA Approves New Therapy for Triple Negative Breast Cancer That Has Spread, Not Responded to Other Treatments". U.S. Food and Drug Administration (FDA). 22 April 2020. Retrieved 22 April 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  4. 4.0 4.1 "Sacituzumab govitecan". SPS - Specialist Pharmacy Service. 10 February 2016. Retrieved 9 October 2021.
  5. "Sacituzumab govitecan (Trodelvy) Use During Pregnancy". Drugs.com. Retrieved 9 October 2021.
  6. "Availability of Trodelvy for European triple negative breast cancer patients". www.europarl.europa.eu. Retrieved 9 October 2021.
  7. "Trodelvy Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 9 October 2021.
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 "FDA grants accelerated approval to sacituzumab govitecan-hziy for metastatic triple negative breast cancer". U.S. Food and Drug Administration (FDA). 22 April 2020. Retrieved 23 April 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  9. 9.0 9.1 9.2 9.3 9.4 9.5 "FDA grants regular approval to sacituzumab govitecan for TNBC". U.S. Food and Drug Administration (FDA). 8 April 2021. Retrieved 9 April 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  10. 10.0 10.1 10.2 "FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer". U.S. Food and Drug Administration (FDA). 13 April 2021. Retrieved 13 April 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  11. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. 2015
  12. "Novel Agents are Targeting Drivers of TNBC". www.medpagetoday.com. 28 June 2016.
  13. "Sacituzumab govitecan Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 22 April 2020.
  14. "Sacituzumab govitecan Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 22 April 2020.
  15. "New Therapy Shows Early Promise, Continues to Progress in Triple-Negative Breast Cancer". Cure Today.
  16. "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" (Press release). Immunomedics. 5 February 2016. Retrieved 25 April 2020 – via GlobeNewswire.
  17. World Health Organization (2015). "International nonproprietary names for pharmaceutical substances (INN): proposed INN: list 113". WHO Drug Information. 29 (2): 260–1. hdl:10665/331080.
  18. World Health Organization (2016). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 75". WHO Drug Information. 30 (1): 151–3. hdl:10665/331046.
  19. 19.0 19.1 19.2 "Drug Trial Snapshot: Trodelvy". U.S. Food and Drug Administration (FDA). 22 April 2020. Retrieved 29 April 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  20. "Trodelvy: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 22 April 2020.
  21. 21.0 21.1 21.2 21.3 21.4 21.5 Bardia, Aditya; Mayer, Ingrid A.; Vahdat, Linda T.; Tolaney, Sara M.; Isakoff, Steven J.; Diamond, Jennifer R.; o'Shaughnessy, Joyce; Moroose, Rebecca L.; Santin, Alessandro D.; Abramson, Vandana G.; Shah, Nikita C.; Rugo, Hope S.; Goldenberg, David M.; Sweidan, Ala M.; Iannone, Robert; Washkowitz, Sarah; Sharkey, Robert M.; Wegener, William A.; Kalinsky, Kevin (2019). "Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer". The New England Journal of Medicine. 380 (8): 741–751. doi:10.1056/NEJMoa1814213. PMID 30786188. S2CID 73489970.
  22. "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Retrieved 17 January 2021. Public Domain This article incorporates text from this source, which is in the public domain.

Further reading

External links

Identifiers: