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 language | English (US) |
|---|---|
| Pages (from-to) | 1155-1164 |
| Number of pages | 10 |
| Journal | Future Oncology |
| Volume | 17 |
| Issue number | 10 |
| DOIs | |
| State | Published - 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