Selpercatinib

Last updated

Selpercatinib
Selpercatinib.svg
Clinical data
Trade names Retevmo, Retsevmo
Other namesLOXO-292
AHFS/Drugs.com Monograph
MedlinePlus a620036
License data
Pregnancy
category
  • AU:D [1]
  • Use should be avoided
Routes of
administration 		By mouth
Drug class Tyrosine kinase inhibitor
ATC code
Legal status
Legal status
Identifiers
  • 6-(2-hydroxy-2-methylpropoxy)-4- (6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3- yl)pyrazolo[1,5-a]pyridine-3-carbonitrile
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C29H31N7O3
Molar mass 525.613 g·mol−1
3D model (JSmol)
  • COc1ccc(CN2C3CC2CN(c2ccc(-c4cc(OCC(C)(C)O)cn5ncc(C#N)c45)cn2)C3)cn1
  • InChI=1S/C29H31N7O3/c1-29(2,37)18-39-24-9-25(28-21(10-30)13-33-36(28)17-24)20-5-6-26(31-12-20)34-15-22-8-23(16-34)35(22)14-19-4-7-27(38-3)32-11-19/h4-7,9,11-13,17,22-23,37H,8,14-16,18H2,1-3H3
  • Key:XIIOFHFUYBLOLW-UHFFFAOYSA-N

Selpercatinib, sold under the brand name Retevmo among others, is a medication for the treatment of cancers in people whose tumors have an alteration (mutation or fusion) in a specific gene (RET which is short for "rearranged during transfection"). [6] [7] [9] It is taken by mouth. [6]

Contents

The most common side effects include changes in laboratory tests (including increased liver enzymes, increased blood sugar, decreased white cell and platelet counts, decreased protein level, decreased calcium, increased total cholesterol, increased creatinine, and decreased sodium) dry mouth, diarrhea, high blood pressure, fatigue, edema, rash, and constipation. [6] [9] [10]

Selpercatinib is a kinase inhibitor, meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from growing. [6] [9] Before beginning treatment, the identification of a RET gene alteration must be determined using laboratory testing. [6] [9]

Selpercatinib is the first therapy approved specifically for people with cancer and the RET gene alterations. [9] Selpercatinib received accelerated approval for this indication for patients aged twelve years of age and older in 2020. [9] [11] [12] [10] In June 2024, the US Food and Drug Administration granted traditional approval to selpercatinib for people aged two years of age and older. [13]

Medical uses

In the United States, selpercatinib is indicated for the treatment of: [6]

In the European Union, selpercatinib, as monotherapy, is indicated for the treatment of adults with: [7]

and for the treatment of people aged twelve years of age and older with advanced RET-mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib. [7]

In September 2024, the FDA granted traditional approval to selpercatinib for people aged two years of age and older with advanced or metastatic medullary thyroid cancer with a RET mutation, as detected by an FDA-approved test, who require systemic therapy. [16] Selpercatinib received accelerated approval for this indication for people 12 years of age and older in 2020. [16] In May 2024, the FDA granted accelerated approval for this indication to people aged two years of age and older. [16]

Adverse effects

Selpercatinib can cause serious side effects including liver toxicity, high blood pressure, heart rhythm changes due to prolongation of heart electrical activity (QT prolongation), bleeding, allergic reactions, impaired wound healing and harm to an unborn baby. [6] [9] [10]

Selpercatinib may cause harm to a developing fetus or a newborn baby. [6] [9]

The most common adverse reactions (≥25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common Grade 3 or 4 laboratory abnormalities (≥5%) were decreased lymphocytes, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, and decreased calcium. [13]

History

Selpercatinib received accelerated approval for this indication for patients aged twelve years of age and older in 2020. [9] [17] [12] [10]

Selpercatinib was approved based on the results of the LIBRETTO-001 clinical trial (NCT03157128) involving 702 participants aged 15–92 years with each of the three types of tumors. [9] [12] [10] During the clinical trial, participants received 160 mg selpercatinib orally twice daily until disease progression or unacceptable toxicity. [9] The major efficacy outcome measures were overall response rate (ORR), which reflects the percentage of participants that had a certain amount of tumor shrinkage, and duration of response (DOR). [9] The trial was conducted at 84 sites in the United States, Canada, Australia, Hong Kong, Japan, South Korea, Singapore, Taiwan, Switzerland, Germany, Denmark, Spain, France, the United Kingdom, Italy and Israel. [10] The conversion to regular approval for non-small cell lung cancer was based on data from an additional 172 participants and 18 months of additional follow-up to assess durability of response. [14]

Efficacy for non-small cell lung cancer was evaluated in 105 adult participants with rearranged during transfection (RET) fusion-positive non-small cell lung cancer who were previously treated with platinum chemotherapy. [9] Sixty-four percent of the 105 participants with previously treated non-small cell lung cancer, experienced complete or partial shrinkage of their tumors which lasted more than six months for 81% of them. [10] Out of 39 participants who had never undergone treatment, 84% experienced complete or partial shrinkage of their tumors which lasted more than six months for 58% of them. [10]

Efficacy for medullary thyroid cancer (MTC) was evaluated in participants aged twelve years of age and older with RET-mutant MTC . [9] The study enrolled 143 participants with advanced or metastatic RET-mutant MTC who had been previously treated with cabozantinib, vandetanib or both (types of chemotherapy), and participants with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. [9] Sixty-nine percent of the 55 previously treated participants for MTC experienced complete or partial shrinkage of their tumors which lasted more than 6 months for 76% of them. [10] Out of 88 participants who had never undergone treatment with an approved drug, 73% experienced complete or partial shrinkage of their tumors which lasted more than six months for 61% of them. [10]

Efficacy for rearranged during transfection (RET) fusion-positive thyroid cancer was evaluated in participants aged twelve years of age and older. [9] The study enrolled 19 participants with RET fusion-positive thyroid cancer who were radioactive iodine-refractory (RAI, if an appropriate treatment option) and had received another prior systemic treatment, and eight participants with RET fusion-positive thyroid cancer who were RAI-refractory and had not received any additional therapy. [9] Seventy-nine percent of the 19 previously treated participants with thyroid cancer experienced complete or partial shrinkage of their tumors which lasted more than six months for 87% of them. [10] All eight participants who had not received therapy other than radioactive iodine therapy experienced complete or partial shrinkage of their tumors which lasted more than six months for 75% of them. [10]

Efficacy for locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options was demonstrated in LIBRETTO-001 (NCT03157128), a multicenter, open-label, multi-cohort trial that evaluated 41 participants with RET fusion-positive tumors (other than non-small cell lung cancer and thyroid cancer) with disease progression on or following prior systemic treatment or who had no satisfactory alternative treatment options. [15] The efficacy evaluation was supported by data in 343 participants with RET fusion-positive non-small cell lung cancer and thyroid cancer enrolled in the same trial already described in product labeling. [15] Participants received selpercatinib until disease progression or unacceptable toxicity. [15]

Society and culture

The US Food and Drug Administration (FDA) granted the application for selpercatinib priority review, orphan drug, and breakthrough therapy designations; [9] [18] and granted approval of Retevmo to Loxo Oncology, Inc., a subsidiary of Eli Lilly and Company. [9]

In December 2020, 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 Retsevmo, intended for the treatment of cancers that display rearranged during transfection (RET) gene alterations: RET-fusion positive non-small cell lung cancer, RET-fusion positive thyroid cancer and RET-mutant medullary-thyroid cancer (MTC). [19] The applicant for this medicinal product is Eli Lilly Nederland B.V. Selpercatinib was approved for medical use in the European Union in February 2021. [7]

In June 2024, the Food and Drug Administration granted traditional approval to selpercatinib for people aged two years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). The applicant was Eli Lilly and Company. [13]

Related Research Articles

<span class="mw-page-title-main">Medullary thyroid cancer</span> Malignant thyroid neoplasm originating from C-cells

Medullary thyroid cancer is a form of thyroid carcinoma which originates from the parafollicular cells, which produce the hormone calcitonin. Medullary tumors are the third most common of all thyroid cancers and together make up about 3% of all thyroid cancer cases. MTC was first characterized in 1959.

<span class="mw-page-title-main">Crizotinib</span> ALK inhibitor for treatment of non-small-cell lung cancer

Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). Crizotinib inhibits the c-Met/Hepatocyte growth factor receptor (HGFR) tyrosine kinase, which is involved in the oncogenesis of a number of other histological forms of malignant neoplasms. It also acts as an ALK and ROS1 inhibitor.

<span class="mw-page-title-main">Cabozantinib</span> Chemical compound

Cabozantinib, sold under the brand names Cometriq and Cabometyx among others, is an anti-cancer medication used to treat medullary thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma. It is a small-molecule tyrosine-kinase inhibitor (TKI) of c-Met (HGFR) and VEGFR2, and also inhibits AXL, RET, and FLT3. It was discovered and developed by Exelixis Inc.

<span class="mw-page-title-main">Nivolumab</span> Anticancer medication

Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.

<span class="mw-page-title-main">Pembrolizumab</span> Pharmaceutical drug used in cancer treatment

Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 Inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.

<span class="mw-page-title-main">Atezolizumab</span> Monoclonal anti-PD-L1 antibody

Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).

<span class="mw-page-title-main">Sacituzumab govitecan</span> Antibody-drug conjugate

Sacituzumab govitecan, sold under the brand name Trodelvy by Gilead Sciences, is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate used for the treatment of metastatic triple-negative breast cancer and metastatic urothelial cancer.

Avelumab, sold under the brand name Bavencio, is a fully human monoclonal antibody medication for the treatment of Merkel cell carcinoma, urothelial carcinoma, and renal cell carcinoma.

<span class="mw-page-title-main">Alectinib</span> ALK inhibitor for treatment of non-small-cell lung cancer

Alectinib (INN), sold under the brand name Alecensa, is an anticancer medication that is used to treat non-small-cell lung cancer (NSCLC). It blocks the activity of anaplastic lymphoma kinase (ALK). It is taken by mouth. It was developed by Chugai Pharmaceutical Co. Japan, which is part of the Hoffmann-La Roche group.

<span class="mw-page-title-main">Entrectinib</span> TKI inhibitor used for cancer treatment

Entrectinib, sold under the brand name Rozlytrek, is an anti-cancer medication used to treat ROS1-positive non-small cell lung cancer and NTRK fusion-positive solid tumors. It is a selective tyrosine kinase inhibitor (TKI), of the tropomyosin receptor kinases (TRK) A, B and C, C-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK).

<span class="mw-page-title-main">Capmatinib</span> Chemical compound

Capmatinib, sold under the brand name Tabrecta, is an anticancer medication used for the treatment of metastatic non-small cell lung cancer whose tumors have a mutation that leads to the exon 14 skipping of the MET gene, which codes for the membrane receptor HGFR.

<span class="mw-page-title-main">Lorlatinib</span> Kinase inhibitor for treatment of non-small-cell lung cancer

Lorlatinib, sold under the brand name Lorbrena in the United States, Canada, and Japan, and Lorviqua in the European Union, is an anti-cancer medication used for the treatment of non-small cell lung cancer. It is an orally administered inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1), two enzymes that play a role in the development of cancer. It was developed by Pfizer.

<span class="mw-page-title-main">Erdafitinib</span> Chemical compound

Erdafitinib, sold under the brand name Balversa, is an anti-cancer medication. It is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) used for the treatment of cancer. FGFRs are a subset of tyrosine kinases which are unregulated in some tumors and influence tumor cell differentiation, proliferation, angiogenesis, and cell survival. Astex Pharmaceuticals discovered the drug and licensed it to Janssen Pharmaceuticals for further development.

Cemiplimab, sold under the brand name Libtayo, is a monoclonal antibody medication for the treatment of squamous cell skin cancer. Cemiplimab belongs to a class of drugs that binds to the programmed death receptor-1 (PD-1), blocking the PD-1/PD-L1 pathway.

<span class="mw-page-title-main">Sotorasib</span> Chemical compound

Sotorasib, sold under the brand names Lumakras and Lumykras, is an anti-cancer medication used to treat non-small-cell lung cancer. It targets a specific mutation, G12C, in the protein K-Ras encoded by gene KRAS which is responsible for various forms of cancer. Sotorasib is an inhibitor of the RAS GTPase family.

<span class="mw-page-title-main">Trastuzumab deruxtecan</span> Medication

Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan. It is licensed for the treatment of breast cancer or gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

Pralsetinib, sold under the brand name Gavreto, is a medication approved for RET mutation-positive medullary thyroid cancer (MTC) and RET fusion-positive differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) therapy. Pralsetinib is a tyrosine kinase inhibitor. It is taken by mouth.

<span class="mw-page-title-main">RET inhibitor</span>

RET kinase inhibitors are a type of targeted cancer treatment that block abnormally activated RET proto-oncogene, a protein involved in cell growth. These inhibitors are used to treat cancers like non-small cell lung cancer, medullary thyroid carcinoma, and some types of colorectal and pancreatic cancer.

<span class="mw-page-title-main">Repotrectinib</span> Medication

Repotrectinib, sold under the brand name Augtyro, is an anti-cancer medication used for the treatment of non-small cell lung cancer. It is taken by mouth. Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC.

References

  1. 1 2 "Retevmo APMDS". Therapeutic Goods Administration (TGA). 13 July 2023. Archived from the original on 20 September 2023. Retrieved 10 September 2023.
  2. ↑ "Retevmo (Eli Lilly Australia Pty Ltd)". Therapeutic Goods Administration (TGA). 28 July 2023. Archived from the original on 11 September 2023. Retrieved 10 September 2023.
  3. ↑ "AusPAR: Retevmo". Therapeutic Goods Administration (TGA). 1 February 2024. Archived from the original on 31 March 2024. Retrieved 31 March 2024.
  4. ↑ "Summary Basis of Decision (SBD) for Retevmo". Health Canada. 23 October 2014. Archived from the original on 29 May 2022. Retrieved 29 May 2022.
  5. ↑ "Retsevmo 40 mg hard capsules - Summary of Product Characteristics (SmPC)". (emc). 27 June 2022. Archived from the original on 25 February 2022. Retrieved 22 September 2022.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Retevmo- selpercatinib capsule". DailyMed. Archived from the original on 4 March 2021. Retrieved 31 March 2021.
  7. 1 2 3 4 5 6 7 "Retsevmo EPAR". European Medicines Agency (EMA). 9 December 2020. Archived from the original on 23 April 2021. Retrieved 23 April 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  8. ↑ "Retsevmo Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
  9. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 "FDA Approves First Therapy for Patients with Lung and Thyroid Cancers with a Certain Genetic Mutation or Fusion" (Press release). U.S. Food and Drug Administration (FDA). 8 May 2020. Archived from the original on 9 May 2020. Retrieved 8 May 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "Drug Trials Snapshots: Retevmo". U.S. Food and Drug Administration (FDA). 8 May 2020. Archived from the original on 20 October 2020. Retrieved 1 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  11. ↑ "Drug Approval Package: Retevmo". U.S. Food and Drug Administration (FDA). 7 August 2020. Archived from the original on 18 January 2022. Retrieved 22 September 2022.
  12. 1 2 3 "Lilly Receives U.S. FDA Approval for Retevmo (selpercatinib), the First Therapy Specifically for Patients with Advanced RET-Driven Lung and Thyroid Cancers" (Press release). Eli Lilly and Company. 8 May 2020. Archived from the original on 9 May 2020. Retrieved 8 May 2020– via PR Newswire.
  13. 1 2 3 "FDA approves selpercatinib for RET fusion-positive thyroid cancer". U.S. Food and Drug Administration. 12 June 2024. Archived from the original on 12 June 2024. Retrieved 13 June 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  14. 1 2 "FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive non-small cell lung cancer" (Press release). U.S. Food and Drug Administration (FDA). 21 September 2022. Archived from the original on 22 September 2022. Retrieved 22 September 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  15. 1 2 3 4 "FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors" (Press release). U.S. Food and Drug Administration (FDA). 21 September 2022. Archived from the original on 22 September 2022. Retrieved 22 September 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  16. 1 2 3 "FDA approves selpercatinib for medullary thyroid cancer". U.S. Food and Drug Administration. 27 September 2024. Retrieved 27 September 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  17. ↑ "Drug Approval Package: Retevmo". U.S. Food and Drug Administration (FDA). 7 August 2020. Archived from the original on 18 January 2022. Retrieved 22 September 2022.
  18. ↑ "FDA approves selpercatinib for lung and thyroid cancers with RET gene". U.S. Food and Drug Administration (FDA). 8 May 2020. Archived from the original on 12 May 2020. Retrieved 11 May 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  19. ↑ "Retsevmo: Pending EC decision". European Medicines Agency (EMA). 11 December 2020. Archived from the original on 11 December 2020. Retrieved 11 December 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.