Abstract
BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cancer without standard therapy. We evaluated the safety and efficacy of a combination of the humanized monoclonal antiprogrammed death-1 (PD-1) antibody, carelizumab, with rivoceranib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in patients with advanced EMPD. METHODS: This multicenter, single-arm, phase II trial included 12 patients with EMPD. The primary endpoint is the objective response rate (ORR), defined as the proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 criteria. It is hypothesized that the ORR will be less than 10% if the treatment is ineffective and will reach 35% if effective. Secondary endpoints include progression-free survival (PFS) and safety assessments. Eligible patients are aged ≥18 years, with histologically confirmed advanced EMPD. Treatment consists of carelizumab (200 mg intravenously every 3 weeks) and rivoceranib (250 mg orally once daily), with dose adjustments permitted based on toxicity profiles. RESULTS: Between June 2024 and February 2025, 12 patients were enrolled. One patient withdrew from the trial because of nontreatment-related accidents, and a total of 11 patients completed at least 1 cycle of treatment. The median PFS is 2.4 months (95% CI, 2.1-4.4 months). Among these 11 patients, no patients achieved CR or PR. Six patients (50%) experienced grade 3 adverse events. CONCLUSIONS: This is the first trial evaluating the combination of a PD-1 inhibitor and a VEGFR inhibitor in advanced EMPD. This combination therapy is well tolerated but does not appear to have clinically meaningful activity in advanced EMPD. This trial was registered at the Chinese Clinical Trial number registration: 2400086153.