Brivanib (B) in Advanced Ovarian Cancer (OC): Subset Results of a Phase 2 Randomized Discontinuation Trial (RDT)

ABSTRACT Background Brivanib (B) is an oral once daily selective dual inhibitor of FGF and VEGF signaling with preclinical activity against various tumor types. An RDT assessed B in pts with advanced solid tumors; data showing activity in sarcoma pts were reported previously, and data for the OC pts are presented here. Methods OC pts progressing after previous treatment received open-label B 800 mg QD for a 12-wk lead-in period and were assessed by CT/MRI. Pts with complete (CR) or partial response (PR) continued on open-label B, those with progressive disease (PD) went off study. Pts with stable disease (SD) were randomized 1:1 to B or placebo (P) until PD or intolerance. Pts with PD on P could crossover to open-label B. Endpoints included progression-free survival (PFS) in randomized pts, objective response rate (ORR), disease control rate (DCR = ORR + SD), and safety. Results One hundred twenty-six pts (63% with u003e3 prior systemic regimens; 88% FGF2+ by IHC) entered 12-wk lead-in and received B. At wk 12, 12 pts had PR and 43 pts had SD (ORR 10%; DCR 44%). Three of 18 pts pretreated with bevacizumab (BEV) achieved PR at wk 12. After 12 wks, 49 continued on the study, 10 with PR remained on open-label B; and 39 were randomized to either B (n = 19) or P (n = 20). Two pts with PR were randomized in error. Among randomized pts (n = 39), median PFS was 4 mo for B vs 2 mo for P with HR of 0.54 (90% CI: 0.28-1.03;p = 0.11). Among randomized FGF2+ pts (n = 36), HR was 0.56 (90% CI:0.29-1.07; p = 0.14). In the randomized phase, 3 additional pts achieved PR (overall population: 15 PRs; ORR 12%). The most common (≥5%) grade ≥3 AEs were increased ALT (20%) and AST (14%), fatigue (12%), hyponatremia (9%), asthenia (7%), diarrhea (7%), hypertension (7%), abdominal pain (6%), and decreased appetite (6%). Discontinuation due to treatment-related AE occurred in 13% of pts. Conclusions The observed PFS prolongation with B vs P, ORR and DCR in this RDT indicate clinical activity of B in pts with heavily pretreated OC, including those with prior BEV. The high frequency of FGF2+ pts precluded the assessment of FGF2 as a predictive biomarker. The safety profile was acceptable. These results support further investigation of B in OC, potentially in pts with prior BEV. Disclosure S.B. Kaye: Consultant for Astra Zeneca, Clovis, GSK, Ju0026J, Pfizer Roche advisory boards Received payment from Roche for development of educational presentations L. Siu: Received research funding from Bristol-Myers Squibb J. Jassem: Advisory Board Member for Bristol-Myers Squibb C.M. Rudin: Consultancy for Oncothyreon P.J. Ou0027Dwyer: Research funding and honorarium from Bristol-Myers Squibb Company. C. Baudelet: Employment and stock ownership of Bristol-Myers Squibb Company. A. Chen: Employment and stock ownership of Bristol-Myers Squibb Company. M.J. Ratain: Research funding from Bristol-Myers Squibb Company All other authors have declared no conflicts of interest.