|Pronunciation||rip re' ti nib|
|Drug class||Kinase inhibitor|
|Main uses||Gastrointestinal stromal tumor (GIST)|
|Side effects||Hair loss, tiredness, nausea, abdominal pain, constipation, muscle pain, diarrhea, rash of the palms and soles|
|Interactions||Medications that affect CYP3A|
|Typical dose||150 mg OD|
|Chemical and physical data|
|Molar mass||510.367 g·mol−1|
|3D model (JSmol)|
Ripretinib, sold under the brand name Qinlock, is a medication used to treat gastrointestinal stromal tumor (GIST). It is used in cases that have failed at least 3 other treatments. It is taken by mouth.
Common side effects include hair loss, tiredness, nausea, abdominal pain, constipation, muscle pain, diarrhea, and a rash of the palms and soles known as palmar-plantar erythrodysesthesia syndrome. Other side effects may include skin cancer and poor wound healing. Use during pregnancy may harm the baby. It is a kinase inhibitor.
Ripretinib was approved for medical use in Australia and the United States in 2020. In the United States it costs about 35,000 per month as of 2021. As of 2021 approval is pending in Europe.
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. GIST is type of stomach, bowel, or esophagus tumor.
It is taken at a dose of 150 mg per day.
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).
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. 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 (FDA) granted the application for ripretinib priority review and fast track designations, as well as breakthrough therapy designation and orphan drug designation. The FDA granted approval of Qinlock to Deciphera Pharmaceuticals, Inc.
The FDA collaborated with the Australian Therapeutic Goods Administration (TGA) and Health Canada on the review of the application as part of Project Orbis. The FDA approved ripretinib three months ahead of schedule. As of May 2020[update], the review of the applications was ongoing for the Australian TGA and for Health Canada.
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