Evidence map›Paper›PMID 31345267›Full record

ArticleJournal for immunotherapy of cancer2019

A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses.

Alexandra S Zimmer, Erin Nichols, Ashley Cimino-Mathews, Cody Peer, Liang Cao, Min-Jung Lee, Elise C Kohn, Christina M Annunziata, Stanley Lipkowitz, Jane B Trepel and 6 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02484404 (Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody Durvalumab), which is not on this map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02484404 phase1 / phase2active not recruitingnot on this map

Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody Durvalumab (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Cancers

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2015 to 2027Enrolled268ConditionsColorectal Neoplasms, Breast NeoplasmsArmsOlaparib, Cediranib, Durvalumab
3 · Its place in the literature

Who cites it

68 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Review
  7. Review
  8. Article
  9. Review
  10. Advances in Systemic Therapy for Ovarian Cancer Over the Past Decade: A Clinical and Molecular Perspective.Medical science monitor : international medical journal of experimental and clinical research · 2025
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. PARP Inhibitors in Colorectal Malignancies: A 2023 Update.Reviews on recent clinical trials · 2024
    Review
  18. PARP inhibitors in non-ovarian gynecologic cancers.Therapeutic advances in medical oncology · 2024
    Review
  19. Review
  20. Article

8 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 3 countries.

Alexandra S ZimmerWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. alexandra.zimmer@nih.gov.ORCID 0000-0001-6789-0982
Erin NicholsWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Ashley Cimino-MathewsJohns Hopkins Hospital Department of Pathology, Baltimore, MD, USA.
Cody PeerGenitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Liang CaoGenetics Branch, National Cancer Institute, Bethesda, MD, USA.
Min-Jung LeeDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Elise C KohnWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Christina M AnnunziataWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Stanley LipkowitzWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Jane B TrepelDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Rajni SharmaJohns Hopkins Hospital Department of Oncology, Baltimore, MD, USA.
Lekha MikkilineniWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Margaret Gatti-MaysWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
William D FiggJohns Hopkins Hospital Department of Pathology, Baltimore, MD, USA.
Nicole D HoustonWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Jung-Min LeeWomen's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
National Cancer Institute · USJohns Hopkins Hospital · USDirectorate of Health · IS

Funding

Clinical trials in womens cancersZIABC011584 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ANNUNZIATA, CHRISTINA · 2014 to 2023
$3.1M
NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

backgroundStrategies to improve activity of immune checkpoint inhibitors are needed. We hypothesized enhanced DNA damage by olaparib, a PARP inhibitor, and reduced VEGF signaling by cediranib, a VEGFR1-3 inhibitor, would complement anti-tumor activity of durvalumab, a PD-L1 inhibitor, and the 3-drug combination would be tolerable.

methodsThis phase 1 study tested the 3-drug combination in a 3 + 3 dose escalation. Cediranib was taken intermittently (5 days on/2 days off) at 15 or 20 mg (dose levels 1 and 2, respectively) with durvalumab 1500 mg IV every 4 weeks, and olaparib tablets 300 mg twice daily. The primary end point was the recommended phase 2 dose (RP2D). Response rate, pharmacokinetic (PK), and correlative analyses were secondary endpoints.

resultsNine patients (7 ovarian/1 endometrial/1 triple negative breast cancers, median 3 prior therapies [2-6]) were treated. Grade 3/4 adverse events include hypertension (1/9), anemia (1/9) and lymphopenia (3/9). No patients experienced dose limiting toxicities. The RP2D is cediranib, 20 mg (5 days on/2 days off) with full doses of durvalumab and olaparib. Four patients had partial responses (44%) and 3 had stable disease lasting ≥6 months, yielding a 67% clinical benefit rate. No significant effects on olaparib or cediranib PK parameters from the presence of durvalumab, or the co-administration of cediranib or olaparib were identified. Tumoral PD-L1 expression correlated with clinical benefit but cytokines and peripheral immune subsets did not.

conclusionsThe RP2D is tolerable and has preliminary activity in recurrent women's cancers. A phase 2 expansion study is now enrolling for recurrent ovarian cancer patients.

trial registrationClinicalTrials.gov identifier: NCT02484404. Registered June 29, 2015.

Indexed as

AdultAgedAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenDrug Administration ScheduleEndometrial NeoplasmsFemaleHumansIndolesMiddle AgedNeoplasm Recurrence, LocalOvarian NeoplasmsPhthalazinesPiperazinesQuinazolinesAntibodies, MonoclonalB7-H1 AntigenCD274 protein, humancediranibdurvalumabIndolesolaparibPhthalazinesPiperazinesQuinazolinesImmune checkpoint inhibitorOvarian cancerPARP inhibitorVEGF inhibition

Identifiers

PMID31345267
PMCPMC6657373
OpenAlexW2963384555

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.