Aims: Trebananib (formerly AMG 386), an investigational peptibody, inhibits tumor angiogenesis by blocking angiopoietin-1/-2 and Tie2 receptor interactions. This interim analysis evaluated the tolerability and efficacy of trebananib plus PLD or T in recurrent ovarian cancer.
Methods: The study included four cohorts: trebananib 10 mg/kg plus PLD (A1) and 15 mg/kg plus PLD (A3); trebananib 10 mg/kg plus T (B1) and 15 mg/kg plus T (B3). Cohorts received PLD 50 mg/m2 IV Q4W or T 4 mg/m2 IV QW (3 on/1 off). Dose-limiting toxicities (DLTs) in <33% of 6 or 9 initial patients triggered cohort expansion to n=25. Endpoints included DLT incidence (primary); and adverse events (AEs), pharmacokinetics, and tumor response (secondary).
Results: 72 of 73 enrolled patients received ≥1 dose of trebananib (A1, A3, B1, B3; n=25, 12, 25, 10). One patient in A1 and none in A3 had DLTs; three patients in B1 and none in B3 experienced DLTs. For A1+A3, AEs ≥50% were fatigue, nausea, and peripheral edema; AEs grade ≥3 in more than three patients were ascites (n=5), abdominal pain (n=5), neutropenia (n=5), decreased appetite (n=4), and fatigue (n=4). For B1+B3, AEs ≥50% were fatigue, nausea, peripheral edema, and thrombocytopenia; AEs grade ≥3 in more than three patients were neutropenia (n=5) and ascites (n=4). Trebananib pharmacokinetics increased dose-proportionally; preliminary results suggest that trebananib did not alter PLD or T exposure. Tumor responses for A1, A3, B1, and B3 were 36%, 18%, 17%, and 0% (objective response rate); and n=10, 3, 8, and 2 (CA-125 responders). Median progression-free survival was 8.1 months for A1+A3 and 3.5 months for B1+B3.
Conclusions: In this phase 1b study of women with recurrent ovarian cancer, no DLTs occurred in the trebananib (AMG 386) 15 mg/kg cohorts. The results of this study suggest evidence of antitumor activity, supporting additional studies in this setting.
Funding: This study was funded by Amgen Inc.
© 2012 Amgen Inc.