Ripretinib, sold under the brand name Qinlock, is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

for the treatment of adults with advanced

gastrointestinal stromal tumor 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 ...

(GIST), a type of tumor that originates in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

. It is taken by mouth. Ripretinib inhibits the activity of the kinases KIT and PDGFRA, which helps keep cancer cells from growing. The most common side effects include

alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...

(hair loss), fatigue, nausea, abdominal pain, constipation,

myalgia Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...

(muscle pain), diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (a skin reaction in the palms and soles) and vomiting. Ripretinib was approved for medical use in the United States in May 2020, in Australia in July 2020, and in the European Union in November 2021. 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 In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

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 Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral chemotherapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple receptor tyrosine kin ...

. GIST is type of stomach, bowel, or esophagus tumor.

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. 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). Ripretinib may cause harm to a developing fetus or a newborn baby.

History

Ripretinib was approved for medical use in the United States in May 2020. 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

sunitinib Sunitinib, sold under the brand name Sutent, is a medication used to treat cancer. 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 i ...

, and

regorafenib 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 ...

. 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. 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. After disease progression, participants who were randomized to placebo were given the option of switching to ripretinib. 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. 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. Additional efficacy outcome measures included overall response rate (ORR) by BICR and overall survival (OS). 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). The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) granted the application for ripretinib

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

and

fast track The fast track is an informal English term meaning "the quickest and most direct route to achievement of a goal, as in competing for professional advancement". By definition, it implies that a less direct, slower route also exists. Fast track or F ...

designations, as well as

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...

designation and

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designation. The FDA granted approval of Qinlock to Deciphera Pharmaceuticals, Inc.

Society and culture

Legal status

Ripretinib was approved for medical use in the United States in May 2020, and in Australia in July 2020. 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. The applicant for this medicinal product is Deciphera Pharmaceuticals (Netherlands) B.V. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Ripretinib was approved for medical use in the European Union in November 2021.

Names

Ripretinib is the International nonproprietary name (INN) and the

United States Adopted Name A United States Adopted Name (USAN) is a unique nonproprietary name assigned to a medication marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association (AMA), the United Stat ...

(USAN).

References

External links

* * * * {{Portal bar , Medicine Antineoplastic drugs Cancer treatments Orphan drugs Receptor tyrosine kinase inhibitors