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

8 Citations (Scopus)

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
Pages (from-to)1155-1164
Number of pages10
JournalFuture Oncology
Volume17
Issue number10
DOIs
Publication statusPublished - 2021 Apr

Bibliographical note

Funding Information:
This study is funded by MacroGenics, Inc. D Catenacci reports personal fees from Archer, Astellas Pharma, Bristol-Myers Squibb, Daiichi Sankyo, Five Prime, Foundation Medicine, Guardant Health, Genentech/Roche, Gritstone Oncology, Lilly, Merck, Natera, Pieris Pharmaceuticals, QED Therapeutics, Seattle Genetics, Taiho Pharmaceutical, Tempus Labs and Zymeworks during the conduct of the study. M Rosales is a full-time employee of MacroGenics. HC Chung reports grants and research support from Amgen, BeiGene, Bristol-Myers Squibb/Ono Pharmaceutical, Celltrion Healthcare, Lilly, GlaxoSmithKline, Incyte, Merck Serono, Merck Sharp & Dohme Corp. and Taiho Pharmaceutical; personal fees for consultation from Amgen, BeiGene, Bristol-Myers Squibb, Gloria Pharma, Lilly, Merck Serono, Merck Sharp & Dohme Corp., Taiho Pharmaceutical and Zymeworks; and personal fees for honoraria from Lilly and Merck Serono during the conduct of the study. HH Yoon reports honoraria for advisory board and steering committee from MacroGenics, honoraria for advisory boards from Bristol-Myers Squibb and Zymeworks, and honoraria for steering committees from BeiGene and Merck during the conduct of the study. L Shen reports grants from Beijing Xiantong Biomedical Technology, Beihai Kangcheng (Beijing) Medical Technology, Boehringer Ingelheim, Jacobio Pharmaceuticals, Qilu Pharmaceutical and Zaiding Pharmaceutical (Shanghai); and consulting fees from Harbour BioMed and Merck outside the submitted work. M Moehler reports grants and nonfinancial support from Arbeitsgemeinschaft Internistische Onkologie, German Ministry of Education and Research, the European Organisation for Research and Treatment of Cancer, and German Cancer Aid during the conduct of the study; personal fees from Amgen, Bristol-Myers Squibb, Falk Foundation, Lilly, MCI Group, Merck Serono, Merck Sharp & Dohme Corp., Pfizer and Roche; grants to the university from Amgen, Bristol-Myers Squibb, Merck Serono, Merck Sharp & Dohme Corp. and Pfizer; and nonfinancial support from Amgen and Bristol-Myers Squibb outside the submitted work. Y-K Kang reports consulting fees from ALX Oncology, Amgen, Astellas Pharma, Bristol-Myers Squibb, Daehwa Pharmaceutical, MacroGenics, Merck, Novartis, Ono Pharmaceutical, Surface Oncology, Taiho Pharmaceutical and Zymeworks and during the conduct of this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Funding Information:
This study is funded by MacroGenics, Inc. D Catenacci reports personal fees from Archer, Astellas Pharma, Bristol-Myers Squibb, Daiichi Sankyo, Five Prime, Foundation Medicine, Guardant Health, Genentech/Roche, Gritstone Oncology, Lilly, Merck, Natera, Pieris Pharmaceuticals, QED Therapeutics, Seattle Genetics, Taiho Pharmaceutical, Tempus Labs and Zymeworks during the conduct of the study.

Publisher Copyright:
© 2021 Catenacci D et al.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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