Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

2090 - Phase 1b/2 study to assess the clinical effects of BGB-290 in combination with radiation therapy (RT) and/or temozolomide (TMZ) in patients with first-line or recurrent/refractory glioblastoma


11 Sep 2017


Poster display session


Cytotoxic Therapy;  Clinical Research;  Surgical Oncology;  Radiation Oncology;  Central Nervous System Malignancies


Patrick Wen


Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367


P.Y. Wen1, K. Shih2, D. Schiff3, R. Brachmann4, R. Weitzman4, T. Cloughesy5

Author affiliations

  • 1 Dana-farber Cancer Institute, Harvard Medical School, 02215 - Boston/US
  • 2 Neuro-oncology, Sarah Cannon Research Insititute, 37205 - Nashville/US
  • 3 Neurology, University of Virginia Health System, Charlottesville/US
  • 4 Clinical Development, BeiGene USA, Inc, 94608 - Emeryville/US
  • 5 Neurology-oncology, University of California Los Angeles, Los Angeles/US


Abstract 2090


Poly (ADP-ribose) polymerase (PARP) proteins are a family of DNA binding and repair proteins and are thought to play a key role in the base excision repair of DNA damage generated by TMZ. In glioblastoma (GB) cells, pharmacological modulation of PARP activity increased growth inhibition induced by TMZ in both p53-wild type and-mutant GB cells lowering the TMZ IC50. RT used in the clinical treatment of GB generates mostly single-strand breaks (SSBs). In non-replicating cells PARP inhibition only delays the repair of SSBs induced by radiation with a minimal impact on cell survival. On the contrary, PARP inhibition markedly enhances radiosensitivity of proliferating cells generating double-strand breaks. Thus, PARP inhibitors have the potential to increase the therapeutic index of RT by increasing DNA damage mainly in highly replicating tumor cells, but sparing non-cycling normal tissues. BGB-290, a potent and selective inhibitor of PARP1/2, has demonstrated potent PARP trapping, brain penetrance and antitumor activity in preclinical intracranial xenograft models.

Trial design

This open-label, dose-escalation/dose-expansion Phase 1b/2 study was designed to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effects of BGB-290 at the recommended Phase 2 dose (60 mg PO BID) in combination with RT and/or TMZ. The Phase 1b component will consist of 3 dose-escalation arms. Arm A: BGB-290 will be combined with RT in patients with first-line GB with unmethylated MGMT promoter (‘unmethylated GB’); Arm B: BGB-290 will be combined with both TMZ and RT in patients with first-line unmethylated GB; Arm C: BGB-290 will be combined with increasing doses of TMZ in patients with recurrent/refractory methylated or unmethylated GB. Once a recommended Phase 2 regimen has been established, up to 60 patients may be enrolled in the dose-expansion (Phase 2) cohort for that arm. In Arm C, 2 expansion cohorts with up to 60 patients each may be opened: 1 for unmethylated GB and 1 for methylated GB.

Clinical trial identification

Legal entity responsible for the study

Beigene Ltd.


Beigene Ltd.


P. Wen: Grants, personal fees, and/or non-financial support from Agios, Angiochem, AstraZeneca, Genentech/Roche, GlaxoSmithKline, Immunocellular Therapeutics, Karyopharm, Merck, Novartis, and other biotech/pharma companies outside submitted work. D. Schiff: Grants from Cavion & Celldex, personal fees from VBI, Orbus, Monteris, Genentech-Roche, Heron Pharmaceuticals, Midatech, and Oxigene, outside the submitted work. R. Brachmann: Employee of Beigene USA, Inc. R. Weitzman: Consultant to BeiGene. T. Cloughesy: Personal fees from Pfizer, Tocagen, Roche, Novocure, Nektar, VBL, ABBVIE, Upshire Smith, Notable Labs, Oxigene, NewGen, Agios, Cortice, MedQia, PRoNai,and other pharma/biotech companies, outside the submitted work. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.