Ripretinib Treatment for Gastrointestinal Stromal Tumors

Ripretinib is a next generation kinase inhibitor that appears promising for treatment of GIST

by Dr. C.H. Weaver M.D. 8/2019

Ripretinib, a broad-spectrum KIT and PDGFRα inhibitor whose mutations are known to drive growth of gastrointestinal stromal tumors (GIST) significantly improves survival and delays cancer recurrence in the most heavily pretreated patients.

About GIST

Gastrointestinal stromal tumors (GIST) are cancers affecting the digestive tract or nearby structures within the abdomen occurring in approximately 4,000 to 6,000 individuals each year in the United States. These sarcomas are driven by mutations, the most common of which are in KIT kinase, representing approximately 75% to 80% of cases, or in PDGFRα kinase, representing approximately 5% to 10%.

Current therapies are unable to inhibit the full spectrum of primary and secondary mutations, which drives resistance and disease progression. Estimates for 5-year survival range from 48% to 90%, depending on the stage of the disease at diagnosis.

About Ripretinib

Ripretinib is an investigational KIT and PDGFRα kinase switch control inhibitor. Ripretinib was specifically designed to improve the treatment of patients with GIST by inhibiting a broad spectrum of mutations in KIT and PDGFRα. Ripretinib is a KIT and PDGFRα inhibitor that inhibits initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary D816V exon 17 mutation involved in SM. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation.

The INVICTUS phase 3 clinical study evaluated the safety and effectiveness of ripretinib in 129 patients with advanced GIST whose previous therapies had included at least imatinib, sunitinib, and regorafenib.

Overall ripretinib was well tolerated and 9.4% or ripretinib treated patients responded to treatment. Ripretinib delayed GIST progression on average 6.3 months compared to 1.0 month for no treatment and ripretinib treated patients survived on average 15.1 months.

Based on the positive INVICTUS data, the Company expects to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib in the first quarter of 2020.

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