Utidelone in patients with advanced soft tissue sarcoma refractory to anthracycline and antiangiogenic therapy (UTISARC): a single-arm phase II study

Treatment options remain limited for patients with advanced or metastatic soft tissue sarcoma after failure of both anthracycline-based chemotherapy and antiangiogenic therapy. Utidelone, an epothilone analog, has demonstrated antitumor activity across a broad spectrum of preclinical models and clinical trials. This single-arm, phase II trial was designed to assess the efficacy and safety of utidelone in a heavily pretreated population. This study enrolled patients aged 18 years or older with locally advanced or metastatic soft tissue sarcoma who had previously been treated with anthracycline-based chemotherapy and antiangiogenic tyrosine kinase inhibitors. Participants received utidelone via a 90-minute intravenous infusion at a dose of 30 mg/m² on days 1–5 of each 21-day treatment cycle, continuing until disease progression or the occurrence of unacceptable toxicity. The primary endpoint was median progression-free survival. The secondary endpoints included the objective response rate, overall survival and safety. Between August 2022 and March 2025, a total of 27 patients were included in the study. The median age was 55 years (range, 30–68). There were 15 patients with leiomyosarcoma, 3 with dedifferentiated liposarcoma, 3 with epithelioid sarcoma, 2 with angiosarcoma, and 4 with other types of sarcoma. The median number of prior systemic therapy regimens was 2 (range, 1–4). The median treatment exposure was 5 cycles (range, 1–10). Two patients achieved a partial response, resulting in an objective response rate of 7%. The median progression-free survival was 4.6 months (95% confidence interval, 3.6–5.6). Overall survival data were immature, with only 9 death events (33%) observed. The estimated 12-month overall survival rate was 80%. Most adverse events were grade 1 or 2 in severity. The most frequently observed grade ≥ 3 adverse event was peripheral neuropathy (11%). In this exploratory trial, utidelone demonstrated preliminary antitumor activity and a manageable safety profile in patients with refractory soft tissue sarcoma. Further exploration of novel combination therapies involving utidelone is warranted to enhance its clinical utility. ChiCTR2200062161, registered on July 26, 2022.