368PD - Dose Escalation/Expansion Study to Investigate the Safety, Pharmacokinetics, Food Effect, and Antitumor Activity of BGB-290 in Patients with Advanc...

Date 09 September 2017
Event ESMO 2017 Congress
Session Developmental therapeutics
Topics Pharmacology
Presenter Jason Lickliter
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors J. Lickliter1, L. Mileshkin2, M. Voskoboynik3, M. Millward4, A. Freimund2, T. Meniawy5, T. Tang6, R. Wei6, M. Li7, V. Paton8
  • 1Oncology, Nucleus Network, 3004 - Melbourne/AU
  • 2Oncology, Peter MacCallum Cancer Center, 3002 - Melbourne/AU
  • 3Oncology, Nucleus Network, Melbourne/AU
  • 4Oncology, Clinical Linear Research, 6009 - Nedlands/AU
  • 5Oncology, Linear Clinical Research Limited, 6009 - Nedlands/AU
  • 6Clinical Pharmacology, BeiGene USA, Inc., Emeryville/US
  • 7Clinical Development, BeiGene Co. Ltd, Beijing/CN
  • 8Oncology, BeiGene, Inc, Emeryville/US

Abstract

Background

Poly (ADP-ribose) polymerase 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 PARP1/2 inhibitor with strong PARP-trapping and antitumor activity in both in vitro and in vivo preclinical tumor models harboring BRCA gene mutations or other homologous recombination defects.

Methods

This two-staged study (NCT02361723) consists of a Phase 1A dose-escalation/dose-finding component to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BGB-290 in patients with solid tumors and a two-part Phase 2 component that includes expansion in targeted indications (Part A) and the effect of food on the BGB-290 pharmacokinetic (PK) profile (Part B).

Results

As of 1 May 2017, Phase 1A had completed enrollment (n = 45); 3 patients remain on treatment. Objective responses were observed across the dose range (2.5–120 mg BID). Of the 23 evaluable patients with gynecological cancer, 10 (43%) achieved an objective response per RECIST 1.1 (n = 3 complete; n = 7 partial). More patients with germline BRCA 1/2 mutated ovarian cancer achieved an objective response (n = 7/12, 58%) than patients not carrying the mutation (n = 2/8, 25%). Drug-related adverse events (AEs) reported in ≥ 10% of patients were nausea, fatigue, anemia, vomiting, diarrhea, anorexia and neutropenia. Anemia and neutropenia were the most common drug-related Grade 3 AEs; no Grade 4 drug-related AEs were reported. Three BGB-290-related serious AEs were reported (anemia, n = 2; nausea, n = 1). Four deaths were associated with an AE; however, none were considered drug-related. The BGB-290 RP2D was determined as 60 mg BID and is being evaluated in Phase 2 to determine antitumor activity and food effects. Dose escalation to determine MTD with QD dosing is ongoing.

Conclusions

BGB-290 has demonstrated a favorable safety profile and promising preliminary antitumor activity in phase 1A; phase 2 is ongoing evaluating in patients with ovarian, breast, prostate, gastric and small cell lung cancer.

Clinical trial identification

NCT02361723, January 29, 2015

Legal entity responsible for the study

Beigene Ltd.

Funding

Beigene Ltd.

Disclosure

T. Meniawy: Non-financial support and other from Beigene during the conduct of the study. T. Tang, R. Wei, M. Li, V. Paton: Employee of BeiGene. All other authors have declared no conflicts of interest.