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Ref Type Journal Article
PMID (22921155)
Authors Matulonis UA, Lee J, Lasonde B, Tew WP, Yehwalashet A, Matei D, Behbakht K, Grothusen J, Fleming G, Lee NK, Arnott J, Bray MR, Fletcher G, Brokx RD, Castonguay V, Mackay H, Sidor CF, Oza AM
Title ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer.
URL
Abstract Text The purpose was to assess the activity and side effect profile of ENMD-2076, an oral anti-angiogenic and anti-proliferative kinase inhibitor, in platinum-resistant recurrent epithelial ovarian cancer (EOC), fallopian tube or peritoneal cancer. Archival tumour tissue was obtained for correlative analyses.This was an open-label single-arm Phase II study of single agent ENMD-2076 taken daily orally (PO). The primary objective was to determine the progression free survival (PFS) rate at 6 months of ENMD-2076 in platinum-resistant cancer based on RECIST v1.1. Secondary objectives included response rate (RR), duration of response, overall survival (OS) and safety. An exploratory analysis of archival tissue for mitotic index and angiogenesis was conducted in an attempt to identify a sensitive or resistant patient phenotype.64 patients were enrolled, and the PFS rate at 6 months was 22% with a median time to progression of 3.6 months. The median number of prior regimens was 2. The most common adverse events were fatigue, hypertension and diarrhoea with the most common Grade 3/4 events being hypertension and fatigue. None of the markers of mitotic index or angiogenesis evaluated in the archival tissue samples were predictive of greater benefit or resistance to ENMD-2076 treatment.ENMD-2076 has activity in platinum-resistant ovarian cancer, and observed toxicities were similar to other PO kinase inhibitors. Additional studies with ENMD-2076 are warranted, especially in combination with active chemotherapeutic agents in platinum-resistant patients. Further work to determine appropriate biomarkers for ENMD-2076 should be incorporated into new clinical studies.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
ENMD-2076 ENMD-2076 2 4
Drug Name Trade Name Synonyms Drug Classes Drug Description
ENMD-2076 ENMD 2076|ENMD2076 Aurka Inhibitors 26 FGFR1 Inhibitor 28 FGFR2 Inhibitor 22 FLT3 Inhibitor 65 RET Inhibitor 52 VEGFR2 Inhibitor 37 ENMD-2076 has selective inhibitory activity against Aurora kinase A and FLT3, with reduced potency against RET, KDR (VEGFR2), FGFR1, and FGFR2, preventing angiogenesis and decreasing cell proliferation (PMID: 21177375, PMID: 22921155, PMID: 32154962).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References