A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)–only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer

Rebecca Kristeleit; Irina Davidenko; Vadim Shirinkin; Fatima El-Khouly; Igor Bondarenko; Michael J Goodheart; Vera Gorbunova; Carol A Penning; Jack G Shi; Xiangdong Liu; Robert C Newton; Yufan Zhao; Janet Maleski; Lance Leopold; Russell J Schilder

doi:10.1016/j.ygyno.2017.07.005

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A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)–only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer

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A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)–only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer

Rebecca Kristeleit, Irina Davidenko, Vadim Shirinkin, Fatima El-Khouly, Igor Bondarenko, Michael J Goodheart, Vera Gorbunova, Carol A Penning, Jack G Shi, Xiangdong Liu, …

Gynecologic Oncology, Vol.146(3), pp.484-490

09/2017

DOI: 10.1016/j.ygyno.2017.07.005

PMID: 28698009

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Abstract

Indoleamine 2,3-dioxygenase-1 (IDO1) is a key regulator of immune tolerance in ovarian cancer. This study investigated efficacy and safety of the IDO1 enzyme inhibitor epacadostat versus tamoxifen in patients with biochemical-only recurrence (CA-125 elevation) following complete remission after first-line chemotherapy for advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. In this open-label, phase 2 study (NCT01685255), patients were randomised 1:1 to epacadostat 600mg or tamoxifen 20mg twice daily for successive 28-day cycles and stratified by time since completion of first-line chemotherapy to first CA-125 elevation (3 to <12 or ≥12months). The primary endpoint was investigator-assessed progression-free survival (PFS; RECIST v1.1). Secondary endpoints included CA-125 response (Gynecologic Cancer InterGroup criteria), overall survival, safety, and tolerability. The study was terminated primarily due to slow accrual and lack of evidence of superiority. Median PFS was 3.75months for epacadostat (n=22) versus 5.56months for tamoxifen (n=20; HR, 1.34 [95% CI, 0.58–3.14]; P=0.54). Of evaluable patients, 1 (5.0%) epacadostat and 3 (15.8%) tamoxifen patients had confirmed CA-125 responses. The most common treatment-emergent adverse event was fatigue (epacadostat, 36.4%; tamoxifen, 40.0%). Immune-related adverse events, observed with epacadostat only, were primarily rash (18.2%) and pruritus (9.1%). Epacadostat pharmacokinetics/pharmacodynamics were consistent with its known mechanism of action. IDO1 expression was observed in 94% of archival tumour samples. This first report of immunotherapy evaluation in biochemical-only relapse ovarian cancer and of IDO1 inhibitor monotherapy in ovarian cancer found no significant difference in efficacy between epacadostat and tamoxifen. Epacadostat was generally well tolerated. •Epacadostat monotherapy was evaluated in biochemically recurrent ovarian cancer.•Immune-related adverse events were manageable and predominantly low grade.•No significant efficacy difference between epacadostat and tamoxifen was observed.•IDO1/PD-L1 coexpression supports evaluation of IDO1 plus checkpoint inhibitors.

Epacadostat

IDO1 enzyme inhibitor

Tamoxifen

Ca-125

Ovarian cancer

Details

Title: Subtitle: A randomised, open-label, phase 2 study of the IDO1 inhibitor epacadostat (INCB024360) versus tamoxifen as therapy for biochemically recurrent (CA-125 relapse)–only epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer
Creators: Rebecca Kristeleit - University College London (UCL) Cancer Institute, UCL, London, UK
Irina Davidenko - Clinical Oncological Dispensary #1, Healthcare Department of Krasnodar Region, Krasnodar, Russia
Vadim Shirinkin - Orenburg Regional Clinical Oncology Dispensary, Orenburg, Russia
Fatima El-Khouly - University College London (UCL) Cancer Institute, UCL, London, UK
Igor Bondarenko - MI Dnipropetrovsk City Multidiscipline Clinical Hospital No. 4, SI Dnipropetrovsk Medical Academy under the MOH of Ukraine, Dnipropetrovsk, Ukraine
Michael J Goodheart - University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Vera Gorbunova - N. N. Blokhin Russian Cancer Research, Center of RAMS, Moscow, Russia
Carol A Penning - Incyte Corporation, Wilmington, DE, USA
Jack G Shi - Incyte Corporation, Wilmington, DE, USA
Xiangdong Liu - Incyte Corporation, Wilmington, DE, USA
Robert C Newton - Incyte Corporation, Wilmington, DE, USA
Yufan Zhao - Incyte Corporation, Wilmington, DE, USA
Janet Maleski - Incyte Corporation, Wilmington, DE, USA
Lance Leopold - Incyte Corporation, Wilmington, DE, USA
Russell J Schilder - Thomas Jefferson University, Philadelphia, PA, USA
Resource Type: Journal article
Publication Details: Gynecologic Oncology, Vol.146(3), pp.484-490
DOI: 10.1016/j.ygyno.2017.07.005
PMID: 28698009
NLM abbreviation: Gynecol Oncol
ISSN: 0090-8258
eISSN: 1095-6859
Publisher: Elsevier Inc
Grant note: name: Incyte Corporation
Language: English
Date published: 09/2017
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983930613402771

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