Combined KIT and CTLA-4 Blockade in Patients with Refractory GIST and Other Advanced Sarcomas: A Phase Ib Study of Dasatinib plus Ipilimumab

Supplementary Data

• Supplemental Figure 1 - Synergy of dasatinib and anti-CTLA-4. Using murine GIST mouse, it was observed that treatment with the KIT-targeted dasatinib for 7 days alone or with chronic anti-CTLA-4 alone decreased tumor volume initially; however tumors rapidly re-grew. Mice treated with KIT-targeted TKI for 7 days and chronic anti-CTLA-4 blockade showed augmentation and durability of the initial response. KITV5880+ mice received dasatinib 15mg/kg i.p. bid (Bristol Myers Squibb) on days 1 through 7, with or without anti-CTLA-5 (BioXcell.) Mice were imaged at baseline and serially during therapy using MRI and volumetric analysis was done using Image K software. Anti-CTLA-4 dosing regimen 200 microgram of clone 9H10 i.p. on day 3, then 100 microgram on day 6, 9 and 12, followed by clone 9D (100 micrograms i.p. every 3 days thereafter.)
• Supplemental Table 1 - Table of adverse events grade 1-4, at least possibly related to treatment. All G1-G4 at least possible related toxicity.