Phase 2 vilastobart tumor-activated Fc-enhanced anti-CTLA-4 plus retifanlimab PD-1 blockade in HRD PDAC.

This Phase 2, single-arm, open-label study (EKLAVYA-HRD) tests dual immune checkpoint blockade using vilastobart (XTX101)—a tumor-activated, Fc‑enhanced anti‑CTLA‑4 antibody designed to preferentially activate in the tumor microenvironment and help deplete CTLA‑4–high regulatory T cells—combined with retifanlimab, an anti‑PD‑1 antibody that restores exhausted T‑cell activity. The trial enrolls patients with metastatic pancreatic adenocarcinoma harboring BRCA1/BRCA2/PALB2 deficiency (a clinically important subset where homologous recombination deficiency is enriched but still a minority of PDAC overall) and requires prior platinum chemotherapy, aligning with a population where DNA-damage sensitivity has already been demonstrated. Massachusetts General Hospital runs the study while leveraging drugs from Xilio Therapeutics (vilastobart/XTX101) and Incyte (retifanlimab/Zynyz). Today’s care after platinum for BRCA/PALB2-altered metastatic PDAC typically includes continued sequencing of multi-agent chemotherapy (and PARP inhibition for appropriate germline BRCA1/2 cases), so the commercial/scientific angle is whether a tumor-selective CTLA‑4 approach can make CTLA‑4 + PD‑1 combinations more tolerable and active in an otherwise immunotherapy-resistant disease.