389P - Preliminary results from a subset of patients (pts) with advanced ovarian cancer (OC) in a dose-escalation/expansion study of BGB-A317, an anti-PD-...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Drug Development
Ovarian Cancer
Cancer Immunology and Immunotherapy
Gynaecologic Malignancies
Presenter Tarek Meniawy
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors T. Meniawy1, G. Richardson2, A. Townsend3, J. Desai4, H. Gan5, M. Friedlander6, L. Horvath7, M.B. Jameson8, S. Sandhu9, Z. Wu10, Z. Qin11, K. Kang12, B. Markman13
  • 1Oncology, Linear Clinical Research Limited, 6009 - Nedlands/AU
  • 2Haemotology & Oncology Services, Cabrini Hospital Malvern, Cabrini Hospital Malvern/AU
  • 3Haematology/oncology, Queen Elizabeth Hospital, 5011 - Woodville/AU
  • 4Medical Oncology, Peter MacCallum Cancer Centre, 3000 - Melbourne/AU
  • 5Austin Hospital, Olivia Newton-John Cancer Research Institute, 3084 - Heidelberg/AU
  • 6Medical Oncology, Prince of Wales Hospital, Randwick/AU
  • 7Medical Oncology, Chris O’Brien Lifehouse, Camperdown/AU
  • 8Regional Cancer Center, Waikato Hospital, 3240 - Hamilton/NZ
  • 9Oncology, Peter MacCallum Cancer Center, 3002 - Melbourne/AU
  • 10Clinical Research, BeiGene USA, Inc, Fort Lee/US
  • 11Clinical Research, BeiGene (Beijing) Co. Ltd, Beijing/CN
  • 12Clinical Development, BeiGene (Beijing) Co. Ltd, Beijing/CN
  • 13Department Of Oncology, Monash Cancer Center, Monash Health, 3168 - Melbourne/AU

Abstract

Background

BGB-A317 is a humanized IgG4 anti-PD-1 mAb that blocks PD-L1/L2 binding to PD-1 restoring T-cell-mediated tumor inhibition. The Fc-hinge region has been engineered to preclude FcγR1 mediated binding to macrophages/myeloid-derived suppressor cells (MDSCs). Upregulation of PD-1/L1 and predominance of macrophages and MDSCs have been reported in OC supporting the rationale of evaluating BGB-A317 in pts with OC.

Methods

An open-label, multi-center, dose-escalation/expansion study is being conducted to evaluate the safety, tolerability and anti-tumor activity of BGB-A317 in pts with advanced solid tumors. Pts with histologically confirmed advanced OC were eligible and treated at different dose levels (0.5, 2, 5, 10 mg/kg intravenously [IV] every 2 weeks [Q2W] in dose escalation, or at 2 or 5 mg/kg IV Q2W or Q3W, or 200 mg IV Q3W in dose expansion, or 5 mg/kg IV Q3W in indication expansion). Tumor assessments, including CA125, occurred approximately every 2 months and response was collected according to both RECIST 1.1 and GCIG criteria. Adverse events (AEs) were assessed per NCI-CTCAE v4.03.

Results

As of 6 Mar 2017, 51 pts [median age 62 (19–80) yrs] with recurrent/refractory OC were enrolled. Most pts were Caucasian (88%), all had received ≥1 prior line of anti-cancer treatment (median 3 [1–12]). Median duration of treatment was 68 (22–446) days; 7 pts remain on study. The most common treatment-emergent AEs were nausea (37%), fatigue (28%), and abdominal pain (28%). 49% of pts experienced an AE ≥Grade (Gr) 3; stomatitis (n = 1) and diarrhoea (n = 1) were Gr 3 AEs considered treatment-related by investigators. Mucosal inflammation, pyrexia and colitis were serious AEs considered treatment-related by investigators (n = 1, each). Among 51 evaluable pts, the disease control rate is 43%; 2 PRs have been reported including 1 pt who remains on study and to date has achieved an 89% reduction in target lesions.

Conclusions

BGB-A317 appears to be generally well tolerated in pts with recurrent/refractory OC. The preliminary safety profile and anti-tumor activity are consistent with that observed with other checkpoint inhibitors and support continued investigation of BGB-A317.

Clinical trial identification

NCT02407990, March 26, 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; Non-financial support from Bristol-Myers Squibb outside the submitted work. J. Desai: Honoraria: Bayer, Merck Serono, Novartis. Consulting or advisory role: Amgen, Bayer, Bionomics, Circadian Technologies, Merck Serono, Norvartis. Research funding: GlaxoSmithKline (Inst), Roche-Genentech (Inst), Ventana Medical Systems (Inst). L. Horvath: Clinical trial agreement with budget from Beigene, during the conduct of the study; S. Sandhu: Honoraria: Bristol-Myers Squibb, Merck. Consulting or Advisory: Amgen. Z. Wu: Employee of Beigene USA, Inc. Z. Qin, K. Kang: Employee of BeiGene (Beijing) Co. Ltd. B. Markman: Personal fees from Beigene during the conduct of the study. All other authors have declared no conflicts of interest.