METRIC: A randomized international study of the antibody-drug conjugate glembatumumab vedotin (GV or CDX-011) in patients (pts) with metastatic gpNMB-overexpressing triple-negative breast cancer (TNBC).
2015; Lippincott Williams & Wilkins; Volume: 33; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2015.33.15_suppl.tps1110
ISSN1527-7755
AutoresDenise A. Yardley, Michelle Melisko, Andres Forero, Brooke Daniel, Alberto J. Montero, Troy H. Guthrie, Vikki A. Canfield, Catherine Oakman, Helen K. Chew, Cristiano Ferrario, G. Volas-Redd, Robyn R. Young, N. Lynn Henry, Lynn Aneiro, Yi He, Christopher D. Turner, Thomas A. Davis, Linda T. Vahdat,
Tópico(s)Cancer Cells and Metastasis
ResumoTPS1110 Background: The internalizable transmembrane glycoprotein NMB (gpNMB) is overexpressed in 20% of BC, including 40% of TNBC (Yardley JCO, in press), where it is a poor prognostic marker (Rose CCR 2010). gpNMB enhances tumor invasion and metastasis and promotes angiogenesis in preclinical models. GV is a novel antibody drug conjugate targeting the potent cytotoxin monomethylauristatin E (MMAE) to gpNMB+ tumor cells. In a Phase I/II study (Bendell JCO, 2014) and the Phase II "EMERGE" study (Yardley JCO, in press), GV demonstrated promising activity, particularly in pts with TNBC and gpNMB overexpression, and was well-tolerated (treatment related toxicities: rash, neutropenia and neuropathy). In subset analyses, for GV vs. "investigator's choice" (IC) single-agent chemotherapy, objective response rate (ORR) was 30% (7/23) vs. 9% (1/11) in pts with gpNMB overexpression (in ≥ 25% of tumor epithelium); 18% (5/28) vs. 0% (0/11) in TNBC; and 40% (4/10) vs. 0% (0/6) in gpNMB-overexpressing TNBC, with apparent improvements in progression-free survival (PFS; hazard ratio (HR) = 0.11) and overall survival (OS; HR = 0.14). Methods: The international (US, CA, Aus) "METRIC" study (NCT01997333) is recruiting up to 300 pts with metastatic, gpNMB-overexpressing TNBC. Eligibility criteria include: ≥ 25% of tumor epithelium gpNMB+ by central IHC prescreening of archival tissue; ER and PR < 10% and HER2(-) [0-1+ IHC, or ISH copy number < 4.0 / ratio < 2.0] by local assessment; ECOG 0-1; taxane resistance; anthracycline exposure (if indicated); ≤ 2 chemotherapy regimens for advanced BC; measurable disease; no persistent Grade ≥ 2 toxicity; and capecitabine naive. Pts are randomized (2:1) to GV (1.88 mg/kg IV q 21 days) or capecitabine, a current standard for this population (2500 mg/m2 daily for d1-14, q21 days) until progression or toxicity. Crossover is not permitted. Endpoints are PFS (primary), ORR, duration of response, OS, safety, PK, PD (immune dynamics) and quality of life. Imaging will be centrally assessed per RECIST 1.1. The trial has 85% power to detect a PFS HR of 0.64 with α = 0.05. Clinical trial information: NCT01997333.
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