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[OT1-03-15] The METRIC trial: A randomized international study of the antibody-drug conjugate glembatumumab vedotin (GV or CDX-011) in patients with metastatic gpNMB-overexpressing triple-negative breast cancer (TNBC). Melisko M, Yardley DA, Blackwell K, Forero A, Ma C, Montero A, Daniel BR, Wright G, Fehrenbacher L, Chew H, Ferrario C, Nanda R, Seiler Jr M, Guthrie T, Vance K, Ouellette G, He Y, Bagley RG, Zhang J, Vahdat LT. University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. Sarah Cannon Research Institute/Tennessee Oncology, PLLC. Duke University Medical Center. University of Alabama. Washington University. Cleveland Clinic. Chattanooga Oncology Hematology Associates. Florida Cancer Specialists. Kaiser Permanente. University of California Davis Comprehensive Cancer Center. Segal Cancer Center-Jewish General Hospital. University of Chicago. Crescent City Research Consortium, LLC. Baptist Cancer Institute. Alabama Oncology. Celldex Therapeutics, Inc.. Weill Cornell Medical College. Background: Glycoprotein NMB (gpNMB) is an internalizable transmembrane protein overexpressed in approximately 20% of breast cancer (BC), including approximately 40% of TNBC. gpNMB is a poor prognostic marker in BC (Rose CCR 2010) and preclinically has been implicated in tumor invasion, metastasis, and angiogenesis. GV is a novel antibody-drug conjugate targeting the potent cytotoxin monomethylauristatin E (MMAE) to gpNMB overexpressing cancer cells. In a Phase I/II study and the Phase II "EMERGE" study, GV demonstrated promising activity with TNBC patients (pts) deriving the greatest benefit and exhibiting the highest degree of gpNMB overexpression. GV was well-tolerated with the most frequent treatment-related toxicities consisting of rash, neutropenia, and neuropathy. In subset analyses of the EMERGE trial, objective response rate (ORR) was 30% (7/23) for GV vs. 9% (1/11) for investigator's choice in tumors with gpNMB overexpression (>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 for GV and IC respectively, with apparent improvements in progression-free survival (PFS; hazard ratio (HR) = 0.11) and overall survival (OS; HR = 0.14). Trial design: The METRIC Trial (NCT#01997333) is an international (USA, CA, Aus), two-arm phase II study. Pts are randomized 2:1 to GV (1.88 mg/kg IV q 21 days) or capecitabine, a current standard of care for this population (2,500 mg/m2 daily for d1-14, q21 days) until progression or intolerance. Crossover is not permitted. Eligibility criteria: Key eligibility criteria include: >25% of tumor epithelium gpNMB+ by central immunohistochemistry (IHC) screening of archival tissue; estrogen receptor and progesterone receptor <10% and HER2 negative [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. Specific aims: The primary endpoint is PFS per independent, blinded central review committee according to RECIST 1.1. Secondary endpoints are ORR, duration of response, OS, safety, pharmacokinetics and pharmacodynamics. Exploratory endpoints are quality of life and/or cancer-related pain. Statistical methods and target accrual: The trial has 85% power to detect a PFS HR of 0.64 with two sided α = 0.05. The hypothesized median PFS is 4.0 months for capecitabine and 6.25 months for GV. Target accrual is open for 300 pts. Wednesday, December 9, 2015 5:00 PM Ongoing Clinical Trials: Ongoing Trials -- Targeted Therapies (5:00 PM-7:00 PM) ↓ 海报下载（文件大小：549KB） |
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