HIF inhibition in mRCC: Planned interim analysis of CRLX101 with bevacizumab (bev), a phase 1b/2a.

e15611 Background: VHL is inactivated in most clear cell RCC (ccRCC) giving rise to the HIF hypoxia response program and tumor angiogenesis. Antiangiogenic therapies are active in ccRCC, but resistance develops in all patients (pts). Dual inhibition strategies may be needed to overcome resistance. CRLX101 (Cerulean Pharma, Inc., Cambridge, MA, USA), a nano pharmaceutical formulation of camptothecin, has been shown in pre-clinical models to inhibit HIF. We combined CRLX101 with bev in the treatment of pts with refractory mRCC to determine the safety and the recommended phase 2 dose (RP2D) of the combination, and to determine the therapeutic activity of treatment. Methods: Pts with refractory mRCC (all subtypes) were treated every 2 weeks with bev 10 mg/kg and escalating doses of CRLX101 (12 mg/m2, 15 mg/m2) in a standard 3+3 design with an expansion at the RP2D. Pts were treated until progression, death, or prohibitive toxicity. Adverse events were classified using CTCAE v 4.0. Radiographic results were as...