Phase I clinical trial of combination imatinib and ipilimumab in patients with advanced malignancies.

3054Background: Imatinib mesylate can induce rapid tumor regression, inhibit tumor immunosuppressive mechanisms, and release large amounts of antigenic debris from tumor cell death with subsequent increase in tumor antigen presentation. CTLA-4 blockade and imatinib combination therapy in mouse models of GIST synergistically reduces size of tumors mediated by imatinib-dependent intratumoral accumulation of CD8+ T-cells and suppression of Treg-cells. We hypothesized that combination therapy with imatinib and ipilimumab immunotherapy would be tolerable and may synergistically enhance anti-tumor T-cell activation in patients (pts). Methods: Primary objective of the dose-escalation study (3+3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose of the combination. Eligible pts had metastatic or unresectable, solid tumors. In the expansion cohort, pts were required to have a known KIT mutation. Secondary objectives included evaluation of antitumor activity of the combination b...