A Phase I/II Trial of BNC105P with XXXX in @entity1358 .

@entity1 @entity2239 @entity1358 @entity1495 @entity6826
PURPOSE: BNC105P inhibits tubulin polymerization, and preclinical studies suggest possible synergy with @entity2239 . In this phase I/II study, efficacy and safety of the combination were explored in @entity1 with @entity1358 ( @entity1358 ). EXPERIMENTAL DESIGN: A phase I study in @entity1 with clear cell @entity1358 and any prior number of therapies was conducted using a classical 3 + 3 design to evaluate standard doses of @entity2239 with increasing doses of BNC105P. At the recommended phase II dose (RP2D), @entity1 with clear cell @entity1358 and one to two prior therapies (including >=  1 VEGF-TKI) were randomized to BNC105P with @entity2239 (arm A) or @entity2239 alone (arm B). The primary endpoint of the study was 6-month progression-free survival (6MPFS). Secondary endpoints included response rate, PFS, overall survival, and exploratory biomarker analyses. RESULTS: In the phase I study (N = 15), a dose of BNC105P at 16 mg/m(2) with @entity2239 at 10 mg daily was identified as the RP2D. In the phase II study, 139 @entity1 were randomized, with 69 and 67 evaluable @entity1 in arms A and B, respectively. 6MPFS was similar in the treatment arms (arm A: 33.82% vs. arm B: 30.30%, P = 0.66) and no difference in median PFS was observed (arm A: 4.7 mos vs. arm B: 4.1 mos; P = 0.49). Changes in @entity1495 , @entity6826 , sex hormone-binding globulin, and serum amyloid A protein were associated with clinical outcome with BNC105P. CONCLUSIONS: Although the primary endpoint was not met in an unselected population, correlative studies suggest several biomarkers that warrant further prospective evaluation. Clin Cancer Res; 1-8.   2015 AACR.
