Ripretinib

Last updated

Ripretinib
Ripretinib skeletal.svg
Clinical data
Pronunciationrip re' ti nib
Trade names Qinlock
Other namesDCC-2618
AHFS/Drugs.com Monograph
MedlinePlus a620035
License data
Pregnancy
category
  • AU:D [1]
  • Use should be avoided
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
  • 3-{4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl]-2-fluorophenyl}-1-phenylurea
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C24H21BrFN5O2
Molar mass 510.367 g·mol−1
3D model (JSmol)
  • CCN1C(=O)C(=CC2=C1C=C(NC)N=C2)C1=C(Br)C=C(F)C(NC(=O)NC2=CC=CC=C2)=C1
  • InChI=1S/C24H21BrFN5O2/c1-3-31-21-12-22(27-2)28-13-14(21)9-17(23(31)32)16-10-20(19(26)11-18(16)25)30-24(33)29-15-7-5-4-6-8-15/h4-13H,3H2,1-2H3,(H,27,28)(H2,29,30,33)
  • Key:CEFJVGZHQAGLHS-UHFFFAOYSA-N

Ripretinib, sold under the brand name Qinlock, is a medication for the treatment of adults with advanced gastrointestinal stromal tumor (GIST), a type of tumor that originates in the gastrointestinal tract. [3] [4] It is taken by mouth. [3] [4] Ripretinib inhibits the activity of the kinases KIT and PDGFRA, which helps keep cancer cells from growing. [4]

Contents

The most common side effects include alopecia (hair loss), fatigue, nausea, abdominal pain, constipation, myalgia (muscle pain), diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (a skin reaction in the palms and soles) and vomiting. [4] [5] [6]

Ripretinib was approved for medical use in the United States in May 2020, [3] [4] in Australia in July 2020, [1] and in the European Union in November 2021. [5] Ripretinib is the first new drug specifically approved in the United States as a fourth-line treatment for advanced gastrointestinal stromal tumor (GIST).

Medical uses

Ripretinib is indicated for the treatment of adults with advanced gastrointestinal stromal tumor (GIST), a type of tumor that originates in the gastrointestinal tract, who have received prior treatment with three or more kinase inhibitor therapies, including imatinib. [3] [4] GIST is type of stomach, bowel, or esophagus tumor. [6]

Adverse effects

The most common side effects include alopecia (hair loss), fatigue, nausea, abdominal pain, constipation, myalgia (muscle pain), diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (a skin reaction in the palms and soles) and vomiting. [4] [6]

Ripretinib can also cause serious side effects including skin cancer, hypertension (high blood pressure) and cardiac dysfunction manifested as ejection fraction decrease (when the muscle of the left ventricle of the heart is not pumping as well as normal). [4] [6]

Ripretinib may cause harm to a developing fetus or a newborn baby. [4] [6]

History

Ripretinib was approved for medical use in the United States in May 2020. [4] [7] [8] [6]

The approval of ripretinib was based on the results of an international, multi-center, randomized, double-blind, placebo-controlled clinical trial (INVICTUS/NCT03353753) that enrolled 129 participants with advanced gastrointestinal stromal tumor (GIST) who had received prior treatment with imatinib, sunitinib, and regorafenib. [4] [9] The trial compared participants who were randomized to receive ripretinib to participants who were randomized to receive placebo, to determine whether progression free survival (PFS) – the time from initial treatment in the clinical trial to growth of the cancer or death – was longer in the ripretinib group compared to the placebo group. [4] During treatment in the trial, participants received ripretinib 150 mg or placebo once a day in 28-day cycles, repeated until tumor growth was found (disease progression), or the participant experienced intolerable side effects. [4] [9] After disease progression, participants who were randomized to placebo were given the option of switching to ripretinib. [4] [9] The trial was conducted at 29 sites in the United States, Australia, Belgium, Canada, France, Germany, Italy, the Netherlands, Poland, Singapore, Spain, and the United Kingdom. [6]

The major efficacy outcome measure was progression-free survival (PFS) based on assessment by blinded independent central review (BICR) using modified RECIST 1.1 in which lymph nodes and bone lesions were not target lesions and a progressively growing new tumor nodule within a pre-existing tumor mass must meet specific criteria to be considered unequivocal evidence of progression. [9] Additional efficacy outcome measures included overall response rate (ORR) by BICR and overall survival (OS). [9] The trial demonstrated a statistically significant improvement in PFS for participants in the ripretinib arm compared with those in the placebo arm (HR 0.15; 95% CI: 0.09, 0.25; p<0.0001). [9]

The U.S. Food and Drug Administration (FDA) granted the application for ripretinib priority review and fast track designations, as well as breakthrough therapy designation and orphan drug designation. [4] [10] The FDA granted approval of Qinlock to Deciphera Pharmaceuticals, Inc. [4]

Society and culture

Ripretinib was approved for medical use in the United States in May 2020, [4] and in Australia in July 2020. [1]

On 16 September 2021, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Qinlock, intended for the treatment of advanced gastrointestinal stromal tumour (GIST) in people who have received prior treatment with three or more kinase inhibitors. [11] The applicant for this medicinal product is Deciphera Pharmaceuticals (Netherlands) B.V. [11] Ripretinib was approved for medical use in the European Union in November 2021. [5] [12]

Names

Ripretinib is the International nonproprietary name (INN) and the United States Adopted Name (USAN). [13] [14]

Related Research Articles

<span class="mw-page-title-main">Gastrointestinal stromal tumor</span> Human disease (cancer)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs stain positively for KIT (CD117). Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract.

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

Erlotinib, sold under the brand name Tarceva among others, is a medication used to treat non-small cell lung cancer (NSCLC) and pancreatic cancer. Specifically it is used for NSCLC with mutations in the epidermal growth factor receptor (EGFR) — either an exon 19 deletion (del19) or exon 21 (L858R) substitution mutation — which has spread to other parts of the body. It is taken by mouth.

<span class="mw-page-title-main">Sunitinib</span> Cancer medication

Sunitinib, sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in January 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.

<span class="mw-page-title-main">Lapatinib</span> Cancer medication

Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).

<span class="mw-page-title-main">Olaparib</span> Chemical compound (cancer therapy drug)

Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers.

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

Lenvatinib, sold under the brand name Lenvima among others, is an anti-cancer medication for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases.

Regorafenib, sold under the brand name Stivarga among others, is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK). Regorafenib shows anti-angiogenic activity due to its dual targeted VEGFR2-TIE2 tyrosine kinase inhibition. Since 2009 it was studied as a potential treatment option in multiple tumor types. By 2015 it had two US approvals for advanced cancers.

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

Rucaparib, sold under the brand name Rubraca, is a PARP inhibitor used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1). It is taken by mouth.

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

Selumetinib (INN), sold under the brand name Koselugo, is a medication for the treatment of children, two years of age and older, with neurofibromatosis type I (NF-1), a genetic disorder of the nervous system causing tumors to grow on nerves. It is taken by mouth.

Onyx Pharmaceuticals Inc. has been a biopharmaceutical company headquartered in South San Francisco, California. The company developed and marketed medicines for the treatment of cancer. Onyx was founded in 1992 by Kevin J. Kinsella and Frank McCormick Ph.D., FRS. McCormick served as the chief scientific officer until 1998, while Kinsella was the firm's chairman. In 2009, the company acquired Proteolix, Inc., a private biotechnology company, for $276 million in cash plus additional milestone payments. In January 2012, the company was named "the top biotechnology takeover target in 2012" through an industry survey. Onyx president and chief executive officer (CEO) Tony Coles had said that Onyx liked its prospects as an independent company and was focused on bringing new therapies to patients. However, at the end of August 2013, Amgen announced it was acquiring Onyx in an agreed $10.4 billion deal.

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

Atezolizumab, sold under the brand name Tecentriq, 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, 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.

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

Ribociclib, sold under the brand name Kisqali, is a medication used for the treatment of certain kinds of breast cancer. Ribociclib is a kinase inhibitor. It was developed by Novartis and Astex Pharmaceuticals.

<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">Tucatinib</span> Chemical compound

Tucatinib, sold under the brand name Tukysa, is an anticancer medication used for the treatment of HER2-positive breast cancer. It is a small molecule inhibitor of HER2. It was developed by Array BioPharma and licensed to Cascadian Therapeutics.

<span class="mw-page-title-main">Selinexor</span> Anti-cancer drug

Selinexor sold under the brand name Xpovio among others, is a selective inhibitor of nuclear export used as an anti-cancer medication. It works by blocking the action of exportin 1 and thus blocking the transport of several proteins involved in cancer-cell growth from the cell nucleus to the cytoplasm, which ultimately arrests the cell cycle and leads to apoptosis. It is the first drug with this mechanism of action.

<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">Avapritinib</span> Chemical compound

Avapritinib, sold under the brand name Ayvakit among others, is a medication used for the treatment of advanced systemic mastocytosis and for the treatment of tumors due to one specific rare mutation: it is specifically intended for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) that harbor a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. Avapritinib is a kinase inhibitor.

<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.

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

Selpercatinib, sold under the brand name Retevmo among others, is a medication for the treatment of cancers in people whose tumors have an alteration in a specific gene. It is taken by mouth.

References

  1. 1 2 3 4 "Qinlock Australian Prescription Medicine Decision Summary". Therapeutic Goods Administration (TGA). 21 July 2020. Retrieved 17 August 2020.
  2. ↑ "Summary Basis of Decision (SBD) for Qinlock". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  3. 1 2 3 4 5 "Qinlock- ripretinib tablet". DailyMed. Retrieved 13 February 2022.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 "FDA Approves First Drug for Fourth-Line Treatment of Advanced Gastrointestinal Stromal Tumors". U.S. Food and Drug Administration (FDA) (Press release). 15 May 2020. Retrieved 15 May 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. 1 2 3 4 "Qinlock EPAR". European Medicines Agency (EMA). 14 September 2021. Retrieved 13 February 2022.
  6. 1 2 3 4 5 6 7 "Drug Trial Snapshot: Qinlock". U.S. Food and Drug Administration (FDA). 15 May 2020. Retrieved 2 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  7. ↑ "FDA Grants Full Approval of Deciphera Pharmaceuticals' Qinlock (ripretinib) for the Treatment of Fourth-Line Gastrointestinal Stromal Tumor". Deciphera Pharmaceuticals, Inc. (Press release). 15 May 2020. Retrieved 15 May 2020.
  8. ↑ "Qinlock: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 15 May 2020.
  9. 1 2 3 4 5 6 "FDA approves ripretinib for advanced gastrointestinal stromal tumor". U.S. Food and Drug Administration (FDA). 15 May 2020. Retrieved 18 May 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. ↑ "Ripretinib Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). 2 October 2014. Retrieved 15 May 2020.
  11. 1 2 "Qinlock: Pending EC decision". European Medicines Agency. 16 September 2021. Retrieved 17 September 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  12. ↑ "Qinlock Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  13. ↑ World Health Organization (2019). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 81". WHO Drug Information. 33 (1): 106. hdl: 10665/330896 . License: CC BY-NC-SA 3.0 IGO.
  14. ↑ "Ripretinib" (PDF). United States Adopted Name (USAN) Drug Finder. Retrieved 17 May 2020.

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.