Dostarlimab

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Dostarlimab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetPDCD1
Names
Trade namesJemperli
Other namesTSR-042, WBP-285, dostarlimab-gxly
Clinical data
Drug classImmunotherapy
Main usesMismatch repair deficient (dMMR) recurrent or advanced cancer[1]
Side effectsTiredness, nausea, diarrhea, anemia[1]
Pregnancy
category
Routes of
use
Intravenous
External links
US NLMDostarlimab
Legal
License data
Legal status
Chemical and physical data
FormulaC6420H9832N1690O2014S44
Molar mass144325.73 g·mol−1

Dostarlimab, sold under the brand name Jemperli, is a medication used to treat certain solid tumors such as endometrial cancer.[1] Specifically it is used for mismatch repair deficient (dMMR) recurrent or advanced cancer.[1] Benefits were seen in 44% of cases.[6] It is given by gradual injection into a vein.[6]

Common side effects include tiredness, nausea, diarrhea, and anemia.[1] Other side effects may include joint pain, itching, rash, fever, and low thyroid.[6] Severe side effect may include pneumonitis, colitis and hepatitis due to immune dysfunction.[1] Use during pregnancy may harm the baby.[1] It is a monoclonal antibody which blocks programmed death receptor-1 (PD-1), thus allowing the immune system to kill cancer cells.[1][6]

Dostarlimab was approved for medical use in the United States and Europe in 2021.[1][6] In the United States it costs about 11,400 USD per 500 mg as of 2022.[7] In the United Kingdom this amount costs about £5,900.[8]

Medical uses

Dostarlimab is used to treat adults with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, that has progressed on or following prior treatment with a platinum-containing regimen.[5][1][6]

In 2021, the US Food and Drug Administration (FDA) granted accelerated approval to dostarlimab for adults with mismatch repair deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.[9][10]

Dosage

The dose is 500 mg once every 3 weeks for the first 4 doses and then 1,000 mg every 6 weeks.[6]

Side effects

Serious adverse reactions in >2% of patients included sepsis, acute kidney injury, urinary tract infection, abdominal pain, and pyrexia.[5][1]

Immune-mediated side effects can occur including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.[5][1]

History

Dostarlimab is a PD-1 inhibitor. As of 2020, it was undergoing Phase I/II and Phase III clinical trials.[11][12][13] In 2020, the manufacturer, Tesaro, announced preliminary successful results from the Phase I/II GARNET study.[11][14][15]

In 2020, the GARNET study announced that dostarlimab was demonstrating potential to treat a subset of women with recurrent or advanced endometrial cancer.[16]

In April 2021, dostarlimab was approved for the treatment of recurrent or advanced endometrial cancer with deficient mismatch repair (dMMR), which are genetic abnormalities that disrupt DNA repair.[17]

In April 2021, the Food and Drug Administration granted accelerated approval to dostarlimab-gxly (Jemperli, GlaxoSmithKline).[5] Efficacy was evaluated based on cohort (A1) in GARNET Trial (NCT02715284), a multicenter, multicohort, open-label trial in participants with advanced solid tumors.[5]

A 2022 early clinical study of dostarlimab reported a 100% remission rate in 14 patients who had mismatch repair deficiency in their rectal cancer, a type of genetic mutation that affects only 5-10% of cases.[18]

Society and culture

Dostarlimab is the international nonproprietary name (INN).[19]

Legal status

On 25 February 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 conditional marketing authorization for the medicinal product, intended for the treatment of certain types of recurrent or advanced endometrial cancer.[20] The applicant for this medicinal product is GlaxoSmithKline (Ireland) Limited.[20] Dostarlimab was approved for medical use in the European Union in April 2021.[6]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 "Jemperli- dostarlimab injection". DailyMed. Archived from the original on 1 March 2022. Retrieved 28 April 2021.
  2. 2.0 2.1 "Jemperli APMDS". Therapeutic Goods Administration (TGA). 2 March 2022. Archived from the original on 19 March 2022. Retrieved 5 March 2022.
  3. "Notice: Multiple Additions to the Prescription Drug List (PDL) [2022-01-24]". Health Canada. 24 January 2022. Archived from the original on 29 May 2022. Retrieved 28 May 2022.
  4. "Summary Basis of Decision (SBD) for Jemperli". Health Canada. 23 October 2014. Archived from the original on 29 May 2022. Retrieved 29 May 2022.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 "FDA grants accelerated approval to dostarlimab-gxly for dMMR endometrial cancer". U.S. Food and Drug Administration (FDA) (Press release). 22 April 2021. Archived from the original on 22 April 2021. Retrieved 22 April 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 "Jemperli EPAR". European Medicines Agency (EMA). 24 February 2021. Archived from the original on 14 May 2022. Retrieved 16 July 2021.
  7. "Jemperli Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 13 June 2022. Retrieved 22 July 2022.
  8. "Dostarlimab". SPS - Specialist Pharmacy Service. 16 March 2019. Archived from the original on 11 February 2022. Retrieved 22 July 2022.
  9. "FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors". U.S. Food and Drug Administration (FDA). 18 August 2021. Archived from the original on 18 August 2021. Retrieved 18 August 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  10. "GSK receives FDA accelerated approval for Jemperli (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors". GlaxoSmithKline (Press release). 17 August 2021. Archived from the original on 10 June 2022. Retrieved 18 August 2021.
  11. 11.0 11.1 Clinical trial number NCT02715284 for "A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors (GARNET)" at ClinicalTrials.gov
  12. Clinical trial number NCT03981796 for "A Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients With Recurrent or Primary Advanced Endometrial Cancer (RUBY)" at ClinicalTrials.gov
  13. Clinical trial number NCT03602859 for "A Phase 3 Comparison of Platinum-Based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-Based Therapy as First-Line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST)" at ClinicalTrials.gov
  14. "Data from GARNET study indicates robust activity of dostarlimab in patients with advanced or recurrent endometrial cancer". GSK (Press release). Archived from the original on 27 December 2019. Retrieved 1 January 2020.
  15. Scalea B (28 May 2019). "Dostarlimab Effective in Endometrial Cancer Regardless of MSI Status". Targeted Oncology. Archived from the original on 27 December 2019. Retrieved 1 January 2020.
  16. "GSK Presents New Data from the GARNET Study Demonstrating Potential of Dostarlimab to Treat a Subset of Women with Recurrent or Advanced Endometrial Cancer". Drugs.com. Archived from the original on 26 March 2022. Retrieved 29 April 2020.
  17. "FDA Approves New Immunotherapy for Endometrial Cancer". Medscape. Archived from the original on 22 April 2021. Retrieved 23 April 2021.
  18. Bellware, Kim; Bernstein, Lenny (10 June 2022). "Eye-catching cancer drug trial results have researchers asking: What's next?". Washington Post. ISSN 0190-8286. Archived from the original on 12 June 2022. Retrieved 15 June 2022.
  19. World Health Organization (2019). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 81". WHO Drug Information. 33 (1). hdl:10665/330896.
  20. 20.0 20.1 "Jemperli: Pending EC decision". European Medicines Agency (EMA) (Press release). 25 February 2021. Archived from the original on 23 April 2021. Retrieved 22 April 2021.

External links

External sites:
Identifiers:
  • Clinical trial number NCT02715284 for "Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors (GARNET)" at ClinicalTrials.gov