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Poster display session

2089 - Phase 1b/2 Study to Assess the Safety, Tolerability, and Clinical Activity of BGB-290 in Combination with Temozolomide in Patients with Locally Advanced or Metastatic Solid Tumors

Date

11 Sep 2017

Session

Poster display session

Presenters

Melissa Johnson

Citation

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

Authors

M. Johnson1, B. Benson2, R. Wei3, R. Brachmann2, M.D. Galsky4

Author affiliations

  • 1 Tennessee Oncology, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 2 Clinical Development, BeiGene USA, Inc, 94608 - Emeryville/US
  • 3 Biostatistics, BeiGene USA, Inc, 94608 - Emeryville/US
  • 4 Medical Oncology, Icahn School of Medicine at Mount Sinai, 00 - New York/US
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Resources

Abstract 2089

Background

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 temozolomide (TMZ), a DNA-alkylating agent. PARP inhibitors (PARPis) represent a class of antitumor agents that exert their cytotoxic effects by inhibiting PARP activity. Some PARPis are capable of trapping PARP proteins on DNA, further augmenting cell death. BGB-290 is a potent and selective inhibitor of PARP1/2 and has demonstrated PARP trapping capacity. Synergistic cytotoxicity has been observed in vitro and in vivo when BGB-290 is combined with low dose TMZ.

Trial design

This open-label, Phase 1b/2 dose-escalation/dose-expansion study is designed to evaluate BGB-290 at the recommended Phase 2 dose (60 mg administered orally twice daily [PO BID]) in combination with TMZ in patients with locally advanced and metastatic solid tumors. The phase 1b dose-escalation component will follow a 3 + 3 design to establish the maximum tolerated dose (MTD) of TMZ in combination with BGB-290 in ∼50 patients with solid tumors. Dose escalation will evaluate the safety, tolerability and pharmacokinetics of BGB-290 (60 mg BID) plus escalating doses of TMZ administered once daily (QD) either on Days 1-7 (Arm A) or continuously (Arm B) of each 28-day cycle. The phase 2 component will further evaluate the safety, tolerability and antitumor activity of the recommended combination dose and schedule in ∼20 patients with one of five different tumor types (Table). Enrollment into these expansion cohorts will occur simultaneously and independent of each other. Subjects will continue to receive treatment in 28-day cycles until confirmed disease progression, intolerable toxicity, or discontinuation/withdrawal.Table:

420TiP

Treatment armTumor typeEstimated sample size
Cohort 1Platinum-sensitive high grade epithelial, non-mucinous, ovarian cancer, fallopian cancer or primary peritoneal cancer with either known deleterious or suspected deleterious germline or somatic BRCA1/2 mutation or with DNA HRD20
Cohort 2Triple negative breast cancer with either known deleterious or suspected deleterious germline or somatic BRCA1/2 mutation or with DNA HRD20
Cohort 3Metastatic castration-resistant prostate cancer with either known deleterious or suspected deleterious germline or somatic BRCA1/2 mutation or with documented HRD20
Cohort 4Extended stage small cell lung cancer who have been treated with ≤2 prior regimens20
Cohort 5Gastric or gastroesophageal junction cancer who have been treated with ≤ 2 prior regimens20

Clinical trial identification

Legal entity responsible for the study

Beigene Ltd.

Funding

Beigene Ltd

Disclosure

M. Johnson: Research funding compensation for consulting to the institution from OncoMed, BerGenBio, Lilly, and various Pharm/Biotech companies. Spouse is a contract lobbyist for Astellas and Otsuka Pharmaceuticals. B. Benson, R. Wei: Employee and stock holder of BeiGene USA. R. Brachmann: Employee of BeiGene USA. M.D. Galsky: Consulting fees from Genentech, Merck, Novartis, Astellas, Astra Zeneca, and Bristol-Myers Squibb outside the submitted work; stock options in Dual Therapeutics outside the submitted work.

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