Phase Ib study of AMG 386 combined with either pegylated liposomal doxorubicin (PLD) or topotecan (T) in patients with advanced ovarian cancer.

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5049 Background: AMG 386 is an investigational peptide-Fc fusion protein that inhibits angiogenesis by preventing angiopoietin 1/2 interaction with the Tie2 receptor. We report on an ongoing, open-label study of AMG 386 combined with PLD or T in advanced ovarian cancer. Methods: In part 1 of this 2-part dose de-escalation study, adult patients (pts) with recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer and GOG performance 0 or 1, and ≤ 3 prior chemotherapy regimens received, IV, AMG 386 at 10 mg/kg QW plus PLD at 50 mg/m2 Q4W (Arm A, n = 6 planned) or T at 4 mg/m2 QW (3 on/1 off; Arm B, n = 6 planned) until progression or unacceptable toxicity. Dose-limiting toxicities (DLTs) in ≥ 3 pts in either arm triggers dose de-escalation of AMG 386 to 3 mg/kg; 6 pts to be enrolled at lower dose. Cohort expansion with 19 pts is planned for part 2 of the study if ≤ 1 pt in either arm has a DLT at either AMG 386 dose. The primary endpoint is DLT incidence; secondary endpoints are safety, PK and response per RECIST (ORR) or CA-125 (GCIG criteria). Results: 12 pts have been enrolled and received ≥ 1 dose of AMG 386 (Arm A/B, n = 6/6). With ≥ 4 weeks follow-up for each pt, there have been no DLTs and no AMG 386 dose de-escalations. 11 pts (Arm A/B, n = 6/5) had AMG 386-related adverse events (AEs): 5 had grade 3 AEs (n = 4/1). There were no grade 4 or 5 AEs. The most common AMG 386-related AEs were nausea (Arm A/B, n = 3/2; no grade 3), fatigue (n = 3/2; grade 3, n = 2/0), rash (n = 3/0; grade 3, n = 2/0), and anemia (n = 0/2; no grade 3). Other key AMG 386-related AEs included hypertension (n = 5/4, no grade 3) and peripheral edema (n = 0/1, grade 3). With median follow-up of 13/21 weeks (Arm A/B), 8 pts were progression-free (n = 5/3); 3 pts had progressed (n = 1/2) and 1 pt (Arm B) died from disease progression. ORR data are not mature. 6 pts had CA-125 responses (Arm A/B, n = 3/3); 1 pt in Arm A had CA-125 progression. Combining AMG 386 with PLD or T did not appear to affect the PK parameters of either agent. Planned cohort expansion to part 2 is underway. Conclusions: Based on these interim results with short follow-up, AMG 386 combined with PLD or T appears tolerable in pts with advanced ovarian cancer. Updated safety and efficacy data will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Nuwan Nanayakkara via Quintiles Amgen, CTI Amgen Amgen, GlaxoSmithKline, Ortho Biotech Amgen