A phase 1b/2, open label, dose-escalation study of margetuximab (M) in combination with pembrolizumab (P) in patients with relapsed/refractory advanced HER2+ gastroesophageal (GEJ) junction or gastric (G) cancer.

TPS219Background: Prognosis for advanced HER2+ GEJ and G cancers remains poor, with median survival just beyond one year. Trastuzumab (T) in combination with chemotherapy is the initial treatment of choice, but therapeutic options targeting HER2 beyond T are poorly defined. M is an Fc-enhanced monoclonal antibody (Mab) to HER2 that recognizes with similar affinity the same epitope as T and whose Fc domain, compared to T, binds with increased affinity to the activating CD16A Fc-receptor (FcR) and decreased affinity to the inhibitory CD32B FcR. Preliminary data shows that M monotherapy has clinical activity against HER2+ tumors in GEJ and G cancer patients previously treated with T or other anti-HER2 agents. P is a Mab that blocks the interaction of the immune checkpoint molecule, PD-1, with its ligands, facilitating tumor cell elimination by releasing tumor-associated T cells from exhaustion. Monotherapy P has demonstrated remarkable and durable clinical activity in a Phase I study. Safety profiles of M an...