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

• Published in: Future oncology (London, England) Vol. 17; no. 10; pp. 1155 - 1164
• Main Authors: Catenacci, Daniel V T, Rosales, Minori, Chung, Hyun Cheol, Yoon, Harry H, Shen, Lin, Moehler, Markus, Kang, Yoon-Koo
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.04.2021
• Subjects: checkpoint inhibitor; first-line therapy; gastric cancer; gastroesophageal adenocarcinoma; gastroesophageal junction cancer; HER2; I-O combination; immuno-oncology; LAG-3; PD-1; first-line therapy; gastric cancer; LAG-3; gastroesophageal adenocarcinoma; gastroesophageal junction cancer; immuno-oncology; I-O combination; HER2; PD-1; checkpoint inhibitor
• ISSN: 1479-6694; 1744-8301; 1744-8301
• DOI: 10.2217/fon-2020-1007

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.