A Drug-Drug Interaction Study to Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Probe Substrate in Patients with Advanced GIST

A Phase 1 Open-label, Multicenter Study to Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Probe Substrate (Repaglinide) in Patients with Advanced Gastrointestinal Stromal Tumors (GIST)

Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Substrate

Inclusion Criteria:

1. Patients ≥18 years of age.
2. Patients must have a histologic diagnosis of GIST.
3. Patients must have GIST that has progressed on or have intolerance to at least 2 lines of prior TKI therapies.
4. Patients must have an Eastern Cooperative Oncology Group performance score of ≤ 2.
5. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
6. Adequate organ and bone marrow function.

Exclusion Criteria:

1. Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose.

2. Prior treatment with ripretinib.

3. Patients who have had prior repaglinide treatment within 14 days prior to Cycle 1 Day 1.

4. History or presence of clinically relevant cardiovascular abnormalities.

5. Gastrointestinal abnormalities including but not limited to:

   • inability to take oral medication,
   • malabsorption syndromes,
   • requirement for intravenous alimentation.

6. Patients who have type 1 or type 2 diabetes.