title: A phase 1b, open-label study of trebananib in combination with paclitaxel and carboplatin in patients with ovarian cancer receiving interval or primary debulking surgery.
abstract: OBJECTIVE
  To evaluate the tolerability, pharmacokinetics and tumour response of first-line trebananib plus paclitaxel and carboplatin followed by trebananib maintenance in high-risk or advanced ovarian cancer.
  
  
  METHODS
  In this open-label phase 1b study, patients received intravenous (IV) trebananib 15 mg/kg administered weekly (QW) plus paclitaxel 175 mg/m(2) once every 3 weeks (Q3W) and carboplatin 6 mg/mL · min Q3W followed by trebananib 15 mg/kg QW monotherapy for 18 months. End-points were dose-limiting toxicities (DLTs; primary); treatment-emergent adverse events (AEs), anti-trebananib antibodies, pharmacokinetics and tumour response (secondary).
  
  
  RESULTS
  Twenty seven patients (interval debulking surgery [IDS], n=13) were enrolled. No DLTs occurred. During the combination therapy phase, AEs (>50%) in patients with IDS were nausea, diarrhoea, fatigue, decreased appetite and thrombocytopenia. In patients with primary debulking surgery (PDS), they were nausea, diarrhoea, fatigue and localised oedema. Grade 4 AEs were neutropenia (IDS, PDS; all n=3) and thrombocytopenia (IDS, PDS; all n=1). No deaths occurred. Toxicity results pertaining to trebananib maintenance were immature. The treatment combination did not markedly affect the pharmacokinetics across agents. In patients with IDS (n=14 after one patient was reassigned from PDS to IDS), 12 patients had a partial response (PR), two patients had stable disease. In patients with PDS (n=4), three patients had a complete response, one patient had a PR.
  
  
  CONCLUSIONS
  In women with ovarian cancer receiving IDS or PDS, IV trebananib 15 mg/kg QW plus paclitaxel and carboplatin appears tolerable. Results suggest that the treatment combination followed by trebananib 15 mg/kg monotherapy is associated with antitumour activity.
authors.affiliation: University Hospitals-KU Leuven, Leuven Cancer Institute, Department of Obstetrics and Gynecology, Herestraat 49, B-3000 Leuven, Belgium. Electronic address: Ignace.Vergote@uz.kuleuven.ac.be.
authors.forename: I
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Vall d'Hebron University Hospital, Medical Oncology Department, and Vall d'Hebron Institute of Oncology (VHIO), Head, Neck, and Gynecological Tumors Group, P. Vall d'Hebron 119-129, Barcelona 08035, Spain. Electronic address: aoaknin@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Oaknin
authors.affiliation: Université Catholique de Louvain, Centre du Cancer, Service d'Oncologie Médicale des Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, Bruxelles 1200, Belgium. Electronic address: jean-francois.baurain@uclouvain.be.
authors.forename: J-F
authors.initials: JF
authors.lastname: Baurain
authors.affiliation: Royal Women's Hospital, Oncology Unit, 20 Flemington Road, Parkville 3052, VIC, Australia. Electronic address: Sumitra.Ananda@mh.org.au.
authors.forename: S
authors.initials: S
authors.lastname: Ananda
authors.affiliation: Western Hospital, Department of Medical Oncology, Oncology Research Level 2 South, Gordon Street, Footscray 3011, VIC, Australia. Electronic address: shirleyS.wong@mh.org.au.
authors.forename: S
authors.initials: S
authors.lastname: Wong
authors.affiliation: Amgen Inc., Department of Biostatistics, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: xsu@amgen.com.
authors.forename: X
authors.initials: X
authors.lastname: Su
authors.affiliation: Amgen Inc., Department of Pharmacokinetics and Drug Metabolism, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: wub@amgen.com.
authors.forename: B
authors.initials: B
authors.lastname: Wu
authors.affiliation: Amgen Inc., Department of Clinical Immunology and Biological Sample Management, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: zhongz@amgen.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Amgen Inc., Department of Clinical Development, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: djwarner@amgen.com.
authors.forename: D
authors.initials: D
authors.lastname: Warner
authors.affiliation: Hospital Universitario Clínico San Carlos, Servicio de Oncologia Medica, Calle del Professor Martín Lagos s/n, Madrid 28040, Spain. Electronic address: Acasado.hcsc@salud.madrid.org.
authors.forename: A
authors.initials: A
authors.lastname: Casado
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D016190:Carboplatin; D017239:Paclitaxel; C551398:trebananib
keywords: Angiogenesis inhibitors; Angiopoietin-1; Angiopoietin-2; Combination drug therapy; Tie2 receptor