Background: BV inhibits VEGF and is approved for progressive GBM following prior therapy. The placental growth factor (PlGF) is a member of the VEGF family and PlGF expression has been shown to correlate with tumor stage and survival in several human malignancies. In cancer patients (pts) PlGF is up-regulated upon treatment with VEGF inhibitors. RO is a humanized IgG1 mAb directed against PlGF that has demonstrated antitumor activity in an orthotopic GBM model. Single agent RO was previously tested in advanced solid tumors. Methods: Eligibility criteria included histologically confirmed GBM with documented radiographic progression upon front line therapy, ≥18 years of age, KPS ≥70, adequate bone marrow reserve and organ function. Prior treatment with VEGF/PLGF targeted therapies was not permitted. Three to six pts were enrolled per dose level (DL), the MTD defined as the dose with DLTs ≤ 1/6 pts during 28-days of cycle 1, using CTCAE v4. Results: A total of 22 pts (16m/6f) have been enrolled in 3 DLs: RO 625mg (4 pts), 1250mg (6), and 2500mg (12) IV every 2 weeks (q2w), each in combination with BV 10mg/kg IV q2w. Median age: 58 years (range 37-72). RO serum concentrations increased proportionally, while serum exposures of BV were similar between all DLs. Two pts experienced a DLT: Meningitis G3 (1250 mg) and cerebral infarction G3 (2500 mg). Most commonly reported adverse events included hypertension (14 pts), headache (11), dysphonia (10), fatigue (6), nasopharyngitis (5), epistaxis (4), constipation (4), nausea (3), and arthralgia (3). Across all DLs tested, the overall response rate by RANO criteria was 22.7%. Conclusions: The tolerability of RO in combination with BV is acceptable; a MTD was not determined. Anti-PlGF treatment does not appear to add on clinical activity observed for single agent BV in recurrent GBM. Clinical trial information: NCT01308684.