Phase 2 ivonescimab PD-1×VEGF bispecific antibody plus intraperitoneal paclitaxel chemotherapy

MD Anderson Cancer Center is running this Phase 2, single-arm study testing ivonescimab (a PD-1 and VEGF-targeted bispecific antibody; developed by Akeso Biopharma and partnered by Summit Therapeutics) combined with intraperitoneal paclitaxel (a microtubule-stabilizing taxane chemotherapy) for unresectable, metastatic, high-grade appendiceal adenocarcinoma after 1–3 prior systemic lines. Patients first undergo laparoscopy with intraperitoneal port placement, then receive IP paclitaxel every 2–3 weeks for cycles 1–5, while ivonescimab is given IV every 2 weeks during cycles 2–4; responders without progression can continue ivonescimab with or without IP paclitaxel every 2–3 weeks for up to 2 years. The key angle is leveraging regional (peritoneal) taxane delivery—aimed at higher local drug exposure—with dual immune checkpoint and anti-angiogenic blockade in a rare, peritoneal-dominant GI cancer where evidence is sparse. Today’s care for unresectable metastatic high-grade appendiceal adenocarcinoma is typically systemic colorectal-type chemotherapy (often fluoropyrimidine + oxaliplatin or irinotecan ± bevacizumab, and sometimes immunotherapy only for MSI-high tumors), with cytoreductive surgery/HIPEC reserved for select patients when feasible; this trial explores whether the combination can control peritoneal disease and potentially increase candidacy for CRS/HIPEC.