How Ripretinib's Mechanism of Action Works in Patients With GIST

Margaret von Mehren, MD, chief in the Division of Sarcoma Medical Oncology and physician director of the Clinical Trials Office at the Fox Chase Cancer Center, discusses ripretinib (DCC-2618) and how it works in patients with heavily pretreated advanced gastrointestinal stromal tumors (GIST).

Ripretinib is unique because of its mechanism of action, according to von Mehren. Most of the other therapies used for the treatment of patients with GIST bind the kinase and try to prevent adenosine triphosphate (ATP) from binding and leading to activation of the kinase. Most kinases require ATP for activation because it blocks the binding.

For ripretinib to become activated, on the other hand, there is a structural change, or activation loop that moves, says von Mehren. The way that this drug works in patients, is it binds the activation loop and the cite it would move into and holds them so that it can’t become activated. She explains the ripretinib works by a different mechanism than most drugs used for these patients.

Ripretinib was investigated in the phase III INVICTUS trial for patients with GIST who have received prior anticancer therapies (NCT03353753).

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