Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

A phase 1/2 study of chemo-immunotherapy with durvalumab (durva) and pegylated liposomal doxorubicin (PLD) in platinum-resistant recurrent ovarian cancer (PROC)

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Roisin O'Cearbhaill

Citation

Annals of Oncology (2018) 29 (suppl_8): viii332-viii358. 10.1093/annonc/mdy285

Authors

R.E. O'Cearbhaill1, A. Wolfer2, P. Disilvestro3, D.M. O'Malley4, P. Sabbatini1, L. Shohara5, P.O. Schwarzenberger5, T. Ricciardi5, M. Macri5, A. Ryan5, R.R. Venhaus5, J.K. Bryan6, P. Wong7, K. Homicsko8, L. Kandalaft9, S. Rusakiewicz9, A. Harari9, B.J. Monk10, G. Coukos11

Author affiliations

  • 1 Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 10065 - New York/US
  • 2 Medical Oncology, University Hospital and University of Lausanne, 1011 - Lausanne/CH
  • 3 Gynecologic Oncology, Women and Infants Hospital of Rhode Island, 02905 - Providence/US
  • 4 Clinical research Gynecologic Oncology, Ohio State University College of Medicine and Ohio State University, James Cancer Center, 43210 - Columbus/US
  • 5 Clinical research, Ludwig Cancer Research, 10017 - New York/US
  • 6 Research, Novella Clinical, 98102 - Seattle/US
  • 7 Ludwig Center For Cancer Immunotherapy, Zuckerman Research Center and Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 8 Oncology, University Hospital and University of Lausanne, 1011 - Lausanne/CH
  • 9 Clinical research, University Hospital of Lausanne and Lausanne Branch, Ludwig Institute for Cancer Research, 1011 - Lausanne/CH
  • 10 Gynecologic Oncology, Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, 85016 - Phoenix/US
  • 11 Medical Oncology, University Hospital of Lausanne and Lausanne Branch, Ludwig Institute for Cancer Research, 1011 - Lausanne/CH
More

Resources

Abstract 2697

Background

Programmed cell death ligand 1 (PD-L1) expression and preliminary evidence of antitumor activity with anti-PD-1 therapy have been reported in ovarian cancer. PLD, a pegylated, liposomal form of doxorubicin, is a standard option for this population; durva is an anti-PD-L1 antibody. The primary objectives of this study are to determine the safety of the combination and to evaluate clinical efficacy by progression-free survival rate at 6 months (PFS6) using RECIST 1.1.

Methods

This is a phase 1/2, multicenter, open-label study (NCT02431559) of durva in patients (pts) with PROC, scheduled to receive PLD. The study includes a dose escalation (phase 1: 3 + 3 design; DLT evaluation over one 28-day cycle; n = 6-18) and a dose expansion (phase 2: n = 41). PLD has been reported to have a 25% PFS6. A sample size of 41 evaluable pts yields 80% power to test the null hypothesis of a PFS6 rate of ≤ 25% against the alternative hypothesis of a PFS rate of ≥ 45% at an alpha level of 0.05 (one-sided). Blood and tumor samples were also collected for assessment of correlative immunologic responses.

Results

First pt dosed: 09Aug2016. As of 05Mar2018, 40 female pts (median age: 65 [32-83] years) were enrolled in phase 2 of the study; each received at least 1 dose of study therapy (PLD 40 mg/m2 + durva 1500 mg Q4W) and are included in the safety analyses. Most frequent (in ≥ 25% pts) treatment-emergent adverse events (AEs, all causality) were palmar-plantar erythrodysesthesia syndrome (PPES)/rash, stomatitis, fatigue, abdominal pain, nausea, pyrexia, and vomiting. Grade 3 treatment-related AEs in ≥ 2 pts included PPES/rash, stomatitis, lymphocyte count decreased, lipase increased, and anemia. As of the cutoff date, 33 pts reached the timepoint for PFS6 assessment. Twelve pts were progression-free at 6 months; PFS6 = 30% (12/40 pts). The remaining data will mature by July 2018, and further improvement in PFS6 may occur. Updated PFS6 and preliminary correlative results will be presented at the meeting.

Conclusions

The combination of durva and PLD in women with PROC appears to have a tolerable safety profile and promising efficacy. PFS6 and translational endpoints are pending additional data.

Clinical trial identification

NCT02431559. May 1st 2015.

Legal entity responsible for the study

Ludwig Institute for Cancer Research.

Funding

Ludwig Institute for Cancer Research, Cancer Research Institute with funding also from VentiRx, and Medimmune. This study was funded in part through the NIH/NCI Support Grant P30 CA008748.

Editorial Acknowledgement

Disclosure

A. Wolfer: Advisory board: AstraZeneca. J.K. Bryan: CMO Novella Clinical, a contract research organization (January 2017-present); Previously CMO VentiRx Pharmaceuticals (2013-2016), with neither equity nor patent ownership on the technology at VentiRx. B.J. Monk: Consultant and speaker: AstraZeneca; Received honoraria for services. All other authors have declared no conflicts of interest.

Resources from the same session

VSV-IFN_-NIS intratumoral (IT) injection: a first-in-human (FIH), phase 1 study of an innovative oncolytic virotherapy, alone and with an anti-PD-L1 antibody, in patients with refractory solid tumors

Presenter: Steven Powell

Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Resources:

Abstract

Vall d’Hebron Institute of Oncology (VHIO) Immuno-Oncology prognostic index (VIO): a new tool for improved patient (pt) selection in Phase 1 (Ph1) trials with Immune Checkpoint Inhibitors (ICI).

Presenter: Cinta Hierro

Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Resources:

Abstract

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings