MAHOGANY: Margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma

Daniel V.T. Catenacci, Minori Rosales, Hyun Cheol Chung, Harry H. Yoon, Lin Shen, Markus Moehler, Yoon Koo Kang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Standard-of-care, first-line therapy for patients with advanced HER2+ gastric/gastroesophageal junction adenocarcinoma is chemotherapy plus trastuzumab, a monoclonal antibody (mAb) targeting HER2. Margetuximab is an Fc-optimized mAb that binds HER2. Retifanlimab, a humanized IgG4 mAb, binds to PD-1 and blocks its interaction with PD-L1/2. Tebotelimab, an IgG4κ bispecific DART® molecule, binds PD-1 and lymphocyte activation gene 3 concomitantly, disrupting these nonredundant inhibitory pathways to further restore exhausted T-cell function. Here, we describe the design and rationale of the randomized, open-label, Phase II/III MAHOGANY trial evaluating margetuximab plus retifanlimab with/without chemotherapy and margetuximab plus tebotelimab with chemotherapy in first-line unresectable metastatic/locally advanced gastroesophageal junction adenocarcinoma. Primary end points include objective response rate, overall survival and safety/tolerability.

Original languageEnglish (US)
Pages (from-to)1155-1164
Number of pages10
JournalFuture Oncology
Volume17
Issue number10
DOIs
StatePublished - Apr 2021

Keywords

  • HER2
  • I-O combination
  • LAG-3
  • PD-1
  • checkpoint inhibitor
  • first-line therapy
  • gastric cancer
  • gastroesophageal adenocarcinoma
  • gastroesophageal junction cancer
  • immuno-oncology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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