Summary
This study consists of a Dose Escalation Part and an Expansion Part.
In the Dose Escalation Part, the maximum tolerated dose of a combination of targeted therapies, pimitespib and imatinib, will be evaluated.
Participants will receive pimitespib orally in 5 consecutive days followed by 2 days off treatment (QD5) on an empty stomach at least 1 hour before or 2 hours after a meal. The doses in this part will be 80mg, 120mg (starting dose), and 160mg). Participants will also receive imatinib orally once daily after a meal and a large glass of water. The doses in this part will be 400mg or 300mg.
The Expansion part consists of 3 arms. Eligible participants will be randomly allocated to one of these three arms.
In Arm A, participants will receive pimitespib in combination with imatinib. Both will be administered as described in the Dose Escalation Part but the doses will be those determined in that Part of the study (the MTD or RD).
In Arm B, participants will receive pimitespib followed by imatinib. Pimitespib will be administered as described in the Dose Escalation Part, with the starting dose of 160mg daily. Imatinib will be administered orally after a meal and with a glass of water, following the discontinuation of pimitespib, starting at 400mg daily.
In Arm C, participants will receive sunitinib, which will be administered orally once daily with a starting dose of 50mg, on a schedule of 4 weeks on treatment followed by 2 weeks off, and will be taken with or without a meal. Arm C will be evaluated as reference data.