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

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.

SUBMITTER: Veitch Z 

PROVIDER: S-EPMC6517396 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature