A phase II study of ENMD-2076 in advanced soft tissue sarcoma (STS)

Zachary Veitch, Alona Zer, Herbert Loong, Samer Salah, Maryam Masood, Abha Gupta, Penelope A. Bradbury, David Hogg, Andrew Wong, Rita Kandel, George S. Charames, Albiruni R. Abdul Razak

Research output: Contribution to journalArticlepeer-review

Abstract

ENMD-2076, an aurora-A kinase inhibitor with anti-angiogenic properties, has shown activity in solid and hematologic malignancies. We investigated oral ENMD-2076 in an open-label, single-arm phase II study using 275 mg daily on a 28-day cycle in patients with advanced soft-tissue sarcomas (STS) receiving ≤1 line of prior therapy. Primary endpoint was 6-month progression-free survival (PFS) with ≤15% indicating no interest, and ≥40% indicating further interest in ENMD-2076. Secondary/exploratory endpoints included clinical benefit (CBR ≥6-months) and objective response (ORR) rates, PFS, OS, safety, and whole-exome sequencing (WES) for potentially associated biomarkers. Overall, 23/25 (92%) patients receiving ENMD-2076 were efficacy evaluable with median follow-up of 14 months (range 2.2–39.5). Common subtypes were leiomyosarcoma (n = 10), undifferentiated pleomorphic sarcoma (n = 3), angiosarcoma (n = 3), and alveolar soft-part sarcoma (n = 3). The 6-month PFS was 20.8% (95% CI:3.2–38.4) with a CBR of 17% (95% CI:1.55–33.23) and ORR of 9% (95% CI:3.08–20.46). Median PFS was 2.5 months (95% CI:2.20–4.47) and OS was 14.1 months (95% CI:6.07–20.07). The most common high-grade treatment-related adverse event was hypertension (60%). WES identified PTPRB mutations in 3/4 patients (p = 0.018) benefiting from ENMD-2076. Although this study failed to meet its primary endpoint, occasional responses and prolonged stable disease was noted. ENMD-2076 evaluation in PTPRB mutated tumors and/or angiosarcoma is warranted.

Original languageEnglish
Article number7390
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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