Phase 1 XmAb541 CLDN6×CD3 T‑cell–engaging bispecific + XmAb808 B7‑H3×CD28 costimulatory bispecific

Xencor’s open-label Phase 1 study (sequential assignment) dose-escalates then dose-expands XmAb541 with XmAb808 to define safety, dose-limiting toxicities, PK, and early antitumor activity (RECIST 1.1) in CLDN6+ high-grade serous ovarian carcinoma (including fallopian tube or primary peritoneal origin) that is locally advanced, recurrent, or metastatic. XmAb541 is a CLDN6×CD3 bispecific that redirects cytotoxic T cells to CLDN6-expressing tumor cells, aiming to concentrate immune killing in an embryonic-antigen target largely absent from normal adult tissue. XmAb808 is a B7‑H3×CD28 “signal 2” costimulatory bispecific designed to activate CD28 only when anchored to B7‑H3 on tumor cells, potentially amplifying T-cell activity while limiting systemic CD28 stimulation. The scientific angle is a rational “signal 1 + signal 2” bispecific pairing (T-cell redirection plus tumor-conditional costimulation) in a biomarker-selected ovarian cancer subset. For recurrent/advanced high-grade serous ovarian cancer today’s care is platinum-based chemo when platinum-sensitive, sequential non-platinum chemo when resistant, bevacizumab in selected settings, PARP inhibitors mainly as maintenance in HRD/BRCA contexts, and later-line options including mirvetuximab soravtansine for FRα-high disease.