A prospective, single-arm, phase 2 trial exploring the use of pamiparib combined with surufatinib as neoadjuvant therapy for advanced, unresectable ovarian cancer (PASSION).

Abstract

5589 Background: Pamiparib is a selective PARP1/2 inhibitor, while surufatinib targets VEGFR1-3, FGFR1, and CSF-1R. We evaluated the efficacy and safety of combining pamiparib and surufatinib in neoadjuvant therapy (NAT) for advanced unresectable ovarian cancer (OC) in a broad, molecularly unselected population. Methods: This phase 2, single-arm study enrolled patients aged 18–70 with newly diagnosed OC in China. Participants received pamiparib (40 mg twice daily, 3 cycles) combined with surufatinib (250 mg twice daily, 2 cycles), followed by interval debulking surgery (IDS) and 4 cycles of platinum-based chemotherapy. Primary endpoint: complete resection (R0). Secondary endpoints: objective response rate (ORR), pathological complete response (pCR), progression-free survival (PFS), overall survival (OS), and safety. Tumor samples before and after treatment were analyzed by transcriptomics, proteomics, and single-cell transcriptomics. Results: Between Nov 2022 and Jan 2025, 32 patients were enrolled, 31 treated, and 1 withdrew. 26 patients completed NAT and underwent IDS, while 5 switched to other chemotherapy due to adverse events. Among resected patients (median age 56, 10 with stage IV), all showed objective responses. R0 was achieved in 24 (92.3%), R1 in 2 (7.7%). Median PFS and OS are not yet reached. Common grade 3/4 adverse events: leukopenia (32.2%), neutropenia (29%), and anemia (29%). No treatment-related deaths were recorded. Post-treatment, B and T cell proportions increased, associated with improved PFS and clinical outcomes. TLS formation was observed, and higher TLS density correlated with better prognosis and reduced tumor biomarkers. Conclusion: Pamiparib and surufatinib show promising efficacy and manageable toxicity in advanced OC, reshaping the tumor microenvironment and promoting immune infiltration. Clinical trial information: NCT05652283 .