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

  • Future Oncol. 2021 Apr;17(10):1155-1164. doi: 10.2217/fon-2020-1007.
Daniel Vt Catenacci  1 ,  Minori Rosales  2 ,  Hyun Cheol Chung  3 ,  Harry H Yoon  4 ,  Lin Shen  5 ,  Markus Moehler  6 ,  Yoon-Koo Kang  7
Affiliations
  • 1. Department of Medicine, Section of Hematology & Oncology, University of Chicago, Chicago, IL 60637, USA.
  • 2. Clinical Research, MacroGenics, Inc., Rockville, MD 20850, USA.
  • 3. Yonsei Cancer Center, University College of Medicine, Seoul 03722, Korea.
  • 4. Mayo Clinic Cancer Center, Rochester, MN 55905, USA.
  • 5. Peking University Cancer Hospital & Institute, Beijing 100142, China.
  • 6. University Medical Center Mainz, Mainz 55131, Germany.
  • 7. Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
PMID: 33263418 DOI: 10.2217/fon-2020-1007
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. Clinical trial registration: NCT04082364 (ClinicalTrials.gov).

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