TY - JOUR
T1 - Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”)
T2 - a randomized multicenter study
AU - Vahdat, Linda T.
AU - Schmid, Peter
AU - Forero-Torres, Andres
AU - Blackwell, Kimberly
AU - Telli, Melinda L.
AU - Melisko, Michelle
AU - Möbus, Volker
AU - Cortes, Javier
AU - Montero, Alberto J.
AU - Ma, Cynthia
AU - Nanda, Rita
AU - Wright, Gail S.
AU - He, Yi
AU - Hawthorne, Thomas
AU - Bagley, Rebecca G.
AU - Halim, Abdel Baset
AU - Turner, Christopher D.
AU - Yardley, Denise A.
N1 - Funding Information:
L.T.V. declares no competing interest; P.S. consulting for the following: Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, Puma and funding from the following: Roche, Genentech, Oncogenex, Novartis; A.F.-T. an employee with Seattle Genetics in November 2018. Received research support paid to the institution from Celldex; K.B. Lilli company, and Tempus labs; M.L.T. advisory role: Celldex (12/2017), Immunomedics, Daiichi Sankyo, Genen-tech, Merck, Celgene, Lilly, AbbVie, Aduro, Pfizer. DSMC: Immunomedics, G1 Therapeutics. Research funding to the institution: Merck, Genentech, AbbVie, Pfizer, PharmaMar, Tesaro, OncoSec, Biothera, Calithera, Vertex, EMD Serono, Bayer; M.M. no competing interest; V.M. declares no competing interest; J.C. Advisor: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim. Honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo. Research funding to the institution: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London. Stock, patents, and intellectual property: MedSIR. Travel, accommodation, expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo.; A.J.M. declares no competing interest. C.M. research support: Puma and Pfizer (clinical trial funding and preclinical studies). Consultant: Puma, Eli Lilly, Pfizer, Novartis (DSMB), Myriad, Seattle Genetics, Agendia, AstraZeneca, Phillips Electronics; R.N. Advisory board: Aduro, AstraZeneca, Ethnics, Celgene, Clovis, Daiichi Sankyo, Inc, Genentech, Immunomedics, MacroGenics, Merck, Novartis, Pfizer, Puma, Seattle Genetics, Syndax. DSMB:G1 Therapeutics. Research Funding: AstraZeneca, Celgene, Corcept Therapeutics, Genentech/Roche, Immunomedics, Merck, OBI Pharm, Inc., Odonate Therapeutics, Pfizer, Seattle Genetics; G.S.W. Received research support paid to the institution from Celldex; D.Y. Research funding: AbbVie, BioMarin, Clovis, Dana Farber Cancer Institute, Eisai, Lilly, G1 Therapeutics, Genentech, Incyte, Innocrin Pharmaceuticals, MacroGenics, MedImmune, Medication, Merck, Merrimack Pharmaceuticals, Nektar, Novartis, NSABP, Odonate Therapeutics, Pfizer, Tesero and US Oncology. Personal financial interest: AbbVie, BMS, Genentech, Immunomedics, Novartis. Y.H., T.H., R.G.B., A-B.H., and C.T. all were employees of Celldex during the conduct of the study and owned company stock.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.
AB - The METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.
UR - http://www.scopus.com/inward/record.url?scp=85106249111&partnerID=8YFLogxK
U2 - 10.1038/s41523-021-00244-6
DO - 10.1038/s41523-021-00244-6
M3 - Article
C2 - 34016993
AN - SCOPUS:85106249111
SN - 2374-4677
VL - 7
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 57
ER -