Drug	Description of study	Results
Nilotinib (NI)	N = 52, retrospective. Imatinib-and/or sunitinib-resistant.	Intolerable in 12%. 10% PR, 37% SD, median PFS 12 weeks and OS 34 weeks.
	N = 53. After failure of second-line SU. Phase I study. NI alone (400 mg bid, n = 18) versus escalating doses of NI + IM (400 mg bid) versus high-dose NI (400 mg bid) + IM 400 mg daily.	Stable disease 68% and median PFS 134 days. 1 durable PR.
Dasatinib	Phase I. n = 19. Two schedules: 5 days on/2 days off or continuous twice daily.	No ORR. 3/19 patients with SD > 3 months and resolution of ascites in 1 patient. Phase II dose: 120 mg twice daily 5on/2off or 70 mg twice daily (CDD).
Sorafenib	Phase II. N = 26. 6 IM-resistant and 20 IM-and SU-resistant. 400 mg oral bid.	13% RECIST PR, 58% SD and 71% disease control rate. Median PFS: 5.3 mo and median OS: 13 mo
	Phase II: placebo-controlled, randomized discontinuation study. N = 3/26 with GIST.	1 patient with minor response. 2 patients with PD < 12 weeks.
	Retrospective study. N = 24. Sorafenib 400 mg oral bid. After failure of IM, SU and NI.	Median days of treatment = 87 days. 20% PR and 50% SD. PFS at 4 months: 25% and OS not reached.
Masatinib	Phase I. n = 19/40 GIST.	No MTD reached. 12 mg/kg/day dose.
	Phase II: n = 30 GIST. IM naïve patients.	1 patient with IM intolerance with PR and 29% of IM-resistant with SD. CR (3%), PR (50%), SD (43%) and PD (3%).
		Median time to response: 5.6 months. Median PFS: 41.3 months and OS of 90% at 2 and 3 years.
Vatalanib	Phase II. N = 15 GIST progressed on IM. Dose = 1,250 mg daily.	2 PR (13%), eight SD for >/= 3 months (53%) and five PD (33%). Median time to progression: 8.5 months (0.0–24.8 mo).
Retaspimycin (IPI-504),	Phase I. n = 38/54 TKI-resistant GIST.	No ORR response, only SD. PET response seen.
	Phase III study.	Closed for toxicity.
Hsp inhibitor
Everolimus (RAD001)	Phase I/II. Everolimus + IM	IM increased the AUC and Cmax of RAD001 via the CYP3A4 and/or P-glycoprotein
	Phase II. IM + RAD001. Evaluated patients who progressed after IM or after IM and SU.	PFS at 4 months was 17.4% (IM only) and 37.1% (IM and SU)
PKC412	Phase I/II trial. N = 19 with IM-resistant GIST. Combination of IM and PKC412.	2/5 evaluable patients with SD at 4 months. PKC decreased dose plasma concentration of PKC412.