Pharmacokinetic (PK) and pharmacodynamic (PD) analysis from a phase I study of PF-03446962, a fully human mab against ALK1, a TGF-beta receptor involved in tumor angiogenesis.

e13606 Background: The proangiogenic activity of Transforming Growth Factor β (TGF-β) on vasculature is exerted by selectively binding to its receptor, activin receptor like kinase 1 (ALK1). PF-03446962 is a fully human mAb against ALK1. Updated results on anti-tumor activity of PF-03446962 from a Phase 1 study in patients (pts) with solid tumors are reported along with PK and PD data. Methods: Effects of PF-03446962 on soluble proteins related to angiogenesis and the TGFβ pathway were investigated with respect to PK, PD, and antitumor activity. Results: 44 pts have been enrolled on 8 dose levels (0.5 - 15 mg/kg). PF-03446962 is administered i.v. on Day 1, 29 and then q 2 weeks. The dose of 10 mg/kg was defined as the maximum tolerated dose. 3 PRs were observed: one HCC resistant to anti-VEGF therapy, one NSCLC and one RCC who received VEGFR2 tyrosine kinase inhibitors (TKIs) as part of the whole previous systemic therapy. SD ≥16 weeks was observed in 7/44 pts. 2/5 HCC pts pre-treated with VEGFR2 TKIs sho...