390P - A phase I study of durvalumab (D) in combination with olaparib (O) and cediranib (C) in recurrent women’s cancers

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Cancer Immunology and Immunotherapy
Gynaecologic Malignancies
Presenter Alexandra Zimmer
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors A. Zimmer1, C. Peer2, L. Cao2, E. Kohn2, S. Lipkowitz3, C. Annunziata3, J. Trepel2, M. Lee2, L. Mikkilineni2, M. Gatti-Mays2, A. Nunes2, S. Soltani2, W.D. Figg2, N. Houston3, E. Nichols3, J. Lee3
  • 1Women's Malignancies Branch, National Cancer Institute National Institutes of HEalth, 20892 - Bethesda/US
  • 2Center For Cancer Research, National Cancer Institute National Institutes of HEalth, Bethesda/US
  • 3Women's Malignancies Branch, National Institutes of Health, Bethesda/US

Abstract

Background

Recent data showed a PARP inhibitor, O and a VEGFR1-3 inhibitor, C together are clinically superior to O alone in recurrent platinum-sensitive ovarian cancer (OvCa). We hypothesized reduced VEGF signaling by C and DNA damage by O may complement anti-tumor activity of immune checkpoint blockade, D. We previously reported the safety data and RP2D of D in combination with O or C. We now report RP2D and PK/PD data of the D+O+C therapy (NCT02484404).

Methods

Eligible patients (pts) with PS 0-1 and good end organ function received D+O+C in a 3 + 3 design. An intermittent C schedule (C; 5 days on/2 days off) at 15 or 20 mg (dose level: 1, 2) was combined with D 1500 mg IV q28 days, and O tablets 300 mg BID. The DLT period was one 28d cycle. Safety was assessed by CTCAEv4.0 and response by RECISTv1.1. Plasma samples were collected for O and C PK analysis and for pro-inflammatory cytokines (IFN-γ, IL-10, IL-12, IL-2, IL-6, IL-8 and TNF-a) pre-treatment and on therapy (cycle 1 day 15 and cycle 3 day 1).

Results

Nine women (median age 59yr [44-73], and median 3 prior therapies [2-6]) were treated. Of the 9 pts, 7 had OvCa, 1 endometrial (EnCa) and 1 triple negative breast Ca. Grade 3/4 AEs include hypertension (1/9), anemia (1/9) and lymphopenia (3/9). No pts experienced DLTs. One patient required dose reduction during cycle 5, for grade 3 anemia. Three PRs were observed in 2 OvCa and 1 EnCa (response rate of 33%, median 5 months [4+-6+]), and 4 had SD (median 5 months [3+-10+]), yielding 78% disease control rate. There were no significant changes in O and C PK parameters caused by D and the co-administration of C or O. All cytokines plasma levels were not changed significantly by the treatment. PD-L1 expression by IHC and immune subsets by flow cytometry are under analysis.

Conclusions

The RP2D for D+O+C (D 1500 mg q28d+O 300 mg tablets BID+C 20 mg 5 days on/2 days off) is tolerable and active in recurrent women’s cancers. A phase II expansion study of D+O+C is to open in OvCa.

Clinical trial identification

(NCT02484404)

Legal entity responsible for the study

National Cancer Institute Center for Cancer Research

Funding

None

Disclosure

All authors have declared no conflicts of interest.