A Two-Part Phase 2 Randomized Study Of Dalantercept And Axitinib Versus Placebo Plus Axitinib In Advanced Renal Cell Carcinoma: Results From The Part 1 Dose Escalation Cohorts

4566 Background: The activity of agents that target the vascular endothelial growth factor (VEGF) pathway in metastatic renal cell cancer (mRCC) may be enhanced in combination with agents that inhibit non-VEGF angiogenesis pathways and may lead to improved outcomes for pts. Activin receptor-like kinase 1 (ALK1) is a type I receptor of the TGFβ superfamily that is expressed on endothelial cells and is involved in blood vessel maturation. Dalantercept (Dal) is an ALK1 receptor-fusion protein that inhibits signaling through ALK1 and has demonstrated additive efficacy with a VEGF receptor (VEGFR) TKI in RCC models. Methods: Part 1 of this randomized 2-part phase 2 study assessed the safety and tolerability of Dal plus axitinib, a VEGFR TKI in pts. with mRCC who had up to 3 prior lines of therapy and determined the recommended phase 2 dose (RP2D). Cohorts of 3-6 pts. each received Dal (0.6, 0.9, or 1.2 mg/kg) SC Q3W and axitinib 5 mg PO BID. An expansion cohort at the RP2D will enroll an additional 10-20 pts. ...