Profile of Margetuximab: Evidence to Date in the Targeted Treatment of Metastatic HER2-positive Breast Cancer

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi:10.3322/caac.21590
   PubMed Web of Science ®Google Scholar
• Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–182. doi:10.1126/science.3798106
   PubMed Web of Science ®Google Scholar
• Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5(1):63–69. doi:10.3816/CBC.2004.n.011
   PubMedGoogle Scholar
• Vogel C, Cobleigh MA, Tripathy D, et al. First-line, single-agent Herceptin (R) (trastuzumab) in metastatic breast cancer. Eur J Cancer. 2001;37(Suppl 1):25–29. doi:10.1016/S0959-8049(00)00405-6
   PubMed Web of Science ®Google Scholar
• Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2019, 382:610–621
   PubMed Web of Science ®Google Scholar
• Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597–609. doi:10.1056/NEJMoa1914609
   PubMed Web of Science ®Google Scholar
• Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(4):519–530. doi:10.1016/S1470-2045(19)30863-0
   PubMed Web of Science ®Google Scholar
• Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724–734. doi:10.1056/NEJMoa1413513
   PubMed Web of Science ®Google Scholar
• Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–1791. doi:10.1056/NEJMoa1209124
   PubMed Web of Science ®Google Scholar
• Krop IE, Lin NU, Blackwell K, et al. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol. 2015;26(1):113–119. doi:10.1093/annonc/mdu486
   PubMed Web of Science ®Google Scholar
• Cortés JKS, Chung W, Im S, Park YH. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): results of the randomized Phase III DESTINY-Breast03 study. Ann Oncol. 2021;32(suppl_5):S1283–S1346. doi:10.1016/j.annonc.2021.08.2087
   Web of Science ®Google Scholar
• Saura C, Oliveira M, Feng YH, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in her2-positive metastatic breast cancer previously treated with >/= 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol. 2020; 38. 3138.
   PubMed Web of Science ®Google Scholar
• Rugo HS, Im SA, Cardoso F, et al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol. 2021;7:573. doi:10.1001/jamaoncol.2020.7932
   PubMed Web of Science ®Google Scholar
• Nordstrom JL, Gorlatov S, Zhang W, et al. Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcgamma receptor binding properties. Breast Cancer Res. 2011;13(6):R123. doi:10.1186/bcr3069
   PubMed Web of Science ®Google Scholar
• Stavenhagen JB, Gorlatov S, Tuaillon N, et al. Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcgamma receptors. Cancer Res. 2007;67(18):8882–8890. doi:10.1158/0008-5472.CAN-07-0696
   PubMed Web of Science ®Google Scholar
• Nimmerjahn F, Ravetch JV. Fcgamma receptors as regulators of immune responses. Nat Rev Immunol. 2008;8(1):34–47. doi:10.1038/nri2206
   PubMed Web of Science ®Google Scholar
• MARGENZA. MARGENZA (Margetuximab-Cmkb) [Package Insert]. Rockville, MD: MacroGenics Inc; 2020.
   Google Scholar
• Musolino A, Naldi N, Dieci MV, et al. Immunoglobulin G fragment C receptor polymorphisms and efficacy of preoperative chemotherapy plus trastuzumab and lapatinib in HER2-positive breast cancer. Pharmacogenomics J. 2016;16(5):472–477. doi:10.1038/tpj.2016.51
   PubMed Web of Science ®Google Scholar
• Lehrnbecher T, Foster CB, Zhu S, et al. Variant genotypes of the low-affinity fcgamma receptors in two control populations and a review of low-affinity fcgamma receptor polymorphisms in control and disease populations. Blood. 1999;94(12):4220–4232. doi:10.1182/blood.V94.12.4220.424k08_4220_4232
   PubMed Web of Science ®Google Scholar
• Koene HR, Kleijer M, Algra J, Roos D. von Dem Borne AE, de Haas M. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood. 1997;90(3):1109–1114.
   PubMed Web of Science ®Google Scholar
• Musolino A, Naldi N, Bortesi B, et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol. 2008;26(11):1789–1796. doi:10.1200/JCO.2007.14.8957
   PubMed Web of Science ®Google Scholar
• Tamura K, Shimizu C, Hojo T, et al. FcgammaR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer. Ann Oncol. 2011;22(6):1302–1307. doi:10.1093/annonc/mdq585
   PubMed Web of Science ®Google Scholar
• Bang YJ, Giaccone G, Im SA, et al. First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol. 2017;28(4):855–861. doi:10.1093/annonc/mdx002
   PubMed Web of Science ®Google Scholar
• Im S-A, Bang Y-J, Oh D-Y, et al. Abstract P6-18-11: long-term responders to single-agent margetuximab, an Fc-modified anti-HER2 monoclonal antibody, in metastatic HER2+ breast cancer patients with prior anti-HER2 therapy. Cancer Res. 2019;79(4 Supplement):P6–18–1–P6–1.
   Web of Science ®Google Scholar
• Pegram MD, Miller K, Tan-Chiu E, et al. A single-arm, open-label, phase 2 study of MGAH22 (margetuximab) [fc-optimized chimeric anti-HER2 monoclonal antibody (mAb)] in patients with relapsed or refractory advanced breast cancer whose tumors express HER2 at the 2+ level by immunohistochemistry and lack evidence of HER2 gene amplification by FISH. J Clin Oncol. 2014;32(15_suppl):TPS671–TPS671.
   Web of Science ®Google Scholar
• Rugo H, Cardoso F, Cortes J, Curigliano G. Phase 3 SOPHIA study of margetuximab (M) + chemotherapy (CTX) vs trastuzumab (T) + CTX in patients (pts) with HER2+ metastatic breast cancer (MBC) after prior anti-HER2 therapies: final overall survival (OS) analysis. SABCS; 2021.
   Google Scholar
• Catenacci DVT, Kang YK, Park H, et al. Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial. Lancet Oncol. 2020;21(8):1066–1076. doi:10.1016/S1470-2045(20)30326-0
   PubMed Web of Science ®Google Scholar
• Catenacci DV, Rosales M, Chung HC, et al. MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. Future Oncol. 2021;17(10):1155–1164. doi:10.2217/fon-2020-1007
   PubMed Web of Science ®Google Scholar
• Luke JJ, Patel MR, Hamilton EP, et al. A Phase I, first-in-human, open-label, dose-escalation study of MGD013, a bispecific DART molecule binding PD-1 and LAG-3, in patients with unresectable or metastatic neoplasms. J Clin Oncol. 2020;38(15_suppl):3004. doi:10.1200/JCO.2020.38.15_suppl.3004
   Web of Science ®Google Scholar
• Loi S, Giobbie-Hurder A, Gombos A, et al. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. Lancet Oncol. 2019;20(3):371–382. doi:10.1016/S1470-2045(18)30812-X
   PubMed Web of Science ®Google Scholar
• Emens LA, Esteva FJ, Beresford M, et al. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol. 2020;21(10):1283–1295. doi:10.1016/S1470-2045(20)30465-4
   PubMed Web of Science ®Google Scholar
• Huober BC, Niilkura N, Niikura N, et al. VP6-2021: iMpassion050: a phase III study of neoadjuvant atezolizumab + pertuzumab + trastuzumab + chemotherapy (neoadj A + PH + CT) in high-risk, HER2-positive early breast cancer (EBC). Ann Oncol. 2021;32(8):1061–1062. doi:10.1016/j.annonc.2021.05.800
   Web of Science ®Google Scholar
• Cortés J, Kim SB, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022386(12):1143–1154. doi:10.1056/NEJMoa2115022
   Google Scholar