Ripretinib (DCC-2618) is an investigational, orally administered kinase switch control inhibitor being developed for the treatment of gastrointestinal stromal tumors (GIST), advanced systemic mastocytosis (ASM), gliomas, and other solid tumors driven by tyrosine-protein kinase KIT (KIT) or platelet derived growth factor alpha (PDGFRα) kinase (where genetic mutations or alterations in these kinases play a crucial role in the biology of these tumors leading to drug-resistance and disease progression). Deciphera is focusing the development of ripretinib in patient subgroups where significant unmet medical need exists despite currently available therapies.

Development Status

Tumor TypeStatus
GIST – 4th Line*Phase 3 Pivotal Study – Ongoing
GIST – 2nd Line**Phase 3 Pivotal Study – Ongoing
GIST, ASM, gliomasPhase 1 Expansion Study – Ongoing
Solid TumorsPhase 1 Expansion Study – Ongoing

*Patients who have received at least three prior therapies including imatinib, sunitinib, and regorafenib

**Patients who progressed on or were intolerant to first-line anticancer treatment with imatinib

Ripretinib in GIST:

Metastatic KIT-driven GIST is a disease characterized by many mutations in KIT, with over 90% of individual KIT-driven GIST patients harboring multiple mutations that drive progression of their disease. The complex heterogeneity of KIT mutations within individual tumors and individual patients is a major cause of resistance to existing therapies.

While approved kinase inhibitors control certain initiating and drug resistance-causing mutations in KIT and PDGFRα, the kinases that drive disease progression in most GIST patients, these approved drugs fail to inhibit all known mutations. Ripretinib was specifically designed to improve the treatment of GIST patients by inhibiting the full spectrum of known mutations in KIT and PDGFRα.

Ripretinib is a KIT and PDGFRα inhibitor that blocks initiating KIT mutations in exons 9, 11, 13, 14, 17, and 18, known to be present in GIST patients, and the D816V exon 17 mutation known to be present in ASM patients. Ripretinib inhibits PDGFRα mutations in exon 18, including the D842V mutation that drives a subset of GIST.

In October 2018 findings from the ongoing Phase 1 trial of ripretinib were presented at the European Society of Medical Oncology (ESMO) 2018 Congress. Further information on the ESMO congress and the ripretinib presentation are available as follows:

Press Release »   |   Publication »

In addition, further information regarding ripretinib and Deciphera’s pipeline is available in the most recent corporate presentation here »

Further information from the ESMO presentation are available here »

Based on the results from the Phase 1 study and the high level of unmet need, Deciphera initiated a pivotal Phase 3 clinical study with ripretinib in fourth-line and fourth-line plus GIST, the “INVICTUS” study, which is fully enrolled. In addition, the Company has initiated a pivotal Phase 3 study with ripretinib in second-line GIST, “the INTRIGUE” study. 

Ripretinib in Advanced Systemic Mastocytosis (ASM):

Approximately 94% of SM patients are reported to have a somatic D816V mutation in KIT. This D816V mutation is a gain-of-function mutation in the KIT activation switch, which leads to unregulated KIT activation. The KIT receptor, which is widely expressed on mast cells, stimulates signaling pathways that control cell growth, differentiation and survival. The gain-of-function mutation, D816V, enables mast cells to proliferate in the absence of normal activation signals. As a broad spectrum KIT inhibitor, ripretinib potently inhibits the D816V mutation. We are enrolling ASM patients within an expansion cohort of our Phase 1 trial.

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