Phase 2 ivonescimab PD-1×VEGF bispecific antibody in previously treated ACC/PPGL

This Phase 2, open-label, multi-cohort study at MD Anderson Cancer Center evaluates ivonescimab given intravenously every 3 weeks in two rare endocrine malignancy populations: unresectable/metastatic adrenocortical carcinoma (ACC) and unresectable pheochromocytoma/paraganglioma (PPGL). Ivonescimab is a dual-targeting bispecific antibody that blocks PD-1 (releasing antitumor T-cell inhibition) and neutralizes VEGF (anti-angiogenesis and potential immune-microenvironment “reprogramming”), aiming to improve response durability versus PD-1 monotherapy in these typically immunotherapy-resistant tumors. The scientific angle is the “two-in-one” IO + anti-VEGF construct being tested in very low-incidence cancers where running large randomized trials is difficult, so efficient single-arm signals can meaningfully shape development strategy. For advanced ACC, systemic therapy commonly centers on EDP-M (etoposide + doxorubicin + cisplatin + mitotane), while progressive PPGL now has FDA-approved belzutifan alongside radiopharmaceutical approaches (such as MIBG or SSTR-targeted PRRT), chemotherapy, and selected TKIs. This trial therefore tests whether a single PD-1×VEGF molecule can generate meaningful activity across two rare, highly vascular endocrine malignancies after prior therapy.