Multicenter phase 1a trial of ivonescimab in patients with advanced solid tumors

Studies showed that VEGF inhibitors could improve therapeutic efficacy of PD-1 antibodies by transforming the immuunsuppressive tumor microenvironment (TME) into a immunoresponsive TME. Ivonescimab is a first-in-class antibody targeting PD-1 and VEGF-A simultaneously. A multicenter phase 1a dose escalation trial in Australia evaluated ivonescimab in patients with advanced solid tumors. The maximum tolerated dose was 20 mg/kg every two weeks. Grade 3 or higher treatment-related adverse events with this dose occurred in 27.5%; especially hypertension, increased transaminase activity, and colitis. The confirmed objective response rate was 25.5% and the disease control rate was 63.8%. Among 19 patients with platinum-resistent ovarian cancer, 5 patients (26.3%) had partial response. Efficacy signals were also observed in patients with colorectal cancer, non-small cell lung cancer, and endometrial cancer. The authors conclude that ivonescimab demonstrated manageable safety profiles and promising efficacy signals in multiple types of advanced solid tumors.