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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

3965 - MEDIOLA: A Phase I/II trial of olaparib (PARP inhibitor) in combination with durvalumab (anti-PD-L1 antibody) in pts with advanced solid tumours – new ovarian cancer cohorts

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Clinical Research

Tumour Site

Ovarian Cancer

Presenters

Richard Penson

Citation

Annals of Oncology (2018) 29 (suppl_8): viii133-viii148. 10.1093/annonc/mdy279

Authors

R.T. Penson1, Y. Drew2, M.J.A. de Jonge3, S. Hong4, Y.H. Park5, A. Wolfer6, J. Brown7, M. Ferguson8, M.E. Gore9, R.H. Alvarez10, B. Kaufman11, C. Gresty12, H.K. Angell12, K. Meyer13, M. Lanasa14, P. Herbolsheimer13, S. Domchek15

Author affiliations

  • 1 ,, Massachusetts General Hospital, 2114 - Boston/US
  • 2 ,, Northern Centre for Cancer Care, Newcastle upon Tyne/GB
  • 3 ,, Erasmus MC Daniel den Hoed Cancer Center, EA - Rotterdam/NL
  • 4 Seoul St Mary's Hospital, Catholic University of Korea, Seoul/KR
  • 5 ,, Samsung Medical Center, Seoul/KR
  • 6 ,, Lausanne University Hospital, Lausanne/CH
  • 7 ,, Beatson West of Scotland Cancer Centre, Glasgow/GB
  • 8 ,, NHS Tayside, Dundee/GB
  • 9 ,, The Royal Marsden Hospital NHS Foundation Trust, London/GB
  • 10 Cancer Treatment Centers Of America, Augusta University, Augusta/US
  • 11 ,, Sheba Medical Center, Ramat Gan/IL
  • 12 ,, AstraZeneca, Cambridge/GB
  • 13 ,, AstraZeneca, Gaithersburg/US
  • 14 ,, AstraZeneca, 20878 - Gaithersburg/US
  • 15 ,, Hospital of the University of Pennsylvania, Philadelphia/US
More

Resources

Abstract 3965

Background

Olaparib (Lynparza®) is a poly(ADP-ribose) polymerase (PARP) inhibitor that prevents the repair of single-strand DNA breaks. Durvalumab (Imfinzi®) is a programmed cell death ligand 1 (anti-PD-L1) inhibitor, which functions by promoting antitumour immune responses. Inhibition of vascular endothelial growth factor (VEGF) has been reported to enhance PARP inhibitor activity. Combinations of immune checkpoint inhibitors and bevacizumab have shown promising results in other tumour types. Here, the efficacy and safety of bevacizumab (anti-VEGF-A antibody) is investigated in combination with olaparib + durvalumab in platinum-sensitive relapsed (PSR) non-gBRCAm ovarian cancer (OC) pts (NCT02734004).

Trial design

Initially, 148 pts were enrolled across several tumour types (small-cell lung cancer, gastric cancer, germline BRCA-mutated [gBRCAm] breast cancer, or PSR gBRCAm OC). Pts received olaparib 300 mg po bid for a 4-wk run-in, followed by olaparib 300 mg po bid and durvalumab 1.5 g IV q4w. Primary endpoints were disease control rate (DCR) at 12 wks, safety and tolerability. Secondary endpoints: pharmacokinetics (PK), DCR at 28 wks, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Tumours were assessed at baseline, 4 wks and every 8 wks thereafter. Enrolment was completed for these initial cohorts, and new PSR OC cohorts (Table) have been added, based on the preliminary results. These cohorts have no olaparib run-in, tumour assessments are performed at baseline and every 8 wks thereafter, bevacizumab 10 mg/kg is given q 2 weeks, and pts with 1–2 prior chemotherapy lines are allowed.Table: 448TiP

New MEDIOLA cohorts

OC cohort nameDrugsPopulationPrimary endpoint
Expansion (N = 80)Olaparib+DurvalumabgBRCAmORR
Doublet (N = 30)Olaparib+Durvalumabnon-gBRCAmDCR 24 wks
Triplet (N = 30)Olaparib+Durvalumab+ Bevacizumabnon-gBRCAmDCR 24 wks

Other endpoints: Safety and tolerability, PK, DCR at 56 wks, ORR, PFS, and OS. Biomarker endpoints: Analysis of tumour-infiltrating lymphocytes and PD-L1 expression.

Clinical trial identification

NCT02734004.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Editorial Acknowledgement

n/a

Disclosure

R.T. Penson: Scientific advisory boards: Amgen Inc., Genentech, Inc., AstraZeneca, Endocyte Inc., Eisai Inc., Vascular Biogenics Ltd, Baxalta Oncology, AbbVie, Clovis Oncology, Tesaro; Research funding: Genentech Inc., ImClone Systems Inc., Endocyte Inc., AstraZeneca, Eisai Inc., Amgen Inc., Vascular Biogenics Ltd; Royalties: BMJ, Blackwell; Publishing Medicine at a Glance, UpToDate Commercial: Advance Medical: Second Medical Opinion. B. Kaufman: Advisory board: AstraZeneca. C. Gresty, H.K. Angell, K. Meyer, M. Lanasa, P. Herbolsheimer: Employee and stockholder: AstraZeneca. S. Domchek: Honoraria: AstraZeneca, Clovis, and Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

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