Utidelone in heavily pretreated metastatic castration-resistant prostate cancer progressing after docetaxel and novel hormonal agents: Results of a completed phase II trial.

5059 Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after both docetaxel and novel hormonal agents (including abiraterone and/or androgen receptor pathway inhibitors ARPIs) have a poor prognosis with limited treatment options. This study aimed to evaluate the efficacy and safety of utidelone, a genetically engineered epothilone analogue with antitumor activity in taxane-resistant cancers, in these patients. Methods: In this prospective, single-arm, phase II clinical trial, eligible male patients were aged 18 to 75 years with mCRPC who had progressed on docetaxel and at least one prior ARPI or abiraterone. Patients received utidelone monotherapy (30 mg/m²/day intravenously for 5 days, every 3 weeks) until progression, intolerable toxicity, or death. Recruitment has been completed with 43 patients enrolled at Sun Yat-sen University Cancer Center from March 23, 2022, to December 10, 2025. The primary endpoint was prostate specific antigen (PSA) response rate, defined as a 50% or greater reduction in serum PSA. Secondary endpoints included radiographic progression-free survival (rPFS) according to PCWG3 criteria, OS, and safety. Results: Analysis was performed on the full cohort. The median age was 66 years, and patients had received a median of 4.0 (range, 2-8) prior lines of treatment. All patients were pre-treated with docetaxel and 97.7% with abiraterone; 90.7% patients had progressed after ARPI, and 14.0% after radionuclide therapy. Visceral metastases were present in 32.6% patients, and 67.4% had de novo metastatic disease. Among 28 patients with available genetic data, BRCA1/2 mutations were identified in 3 (10.7%). By the data cut-off (January 4, 2026), the PSA50 response rate (≥50% decline) was 23.3%, and 32.6% of patients achieved a PSA30 response (≥30% decline). The median rPFS was 6.7 months, and median OS was 11.4 months. Most of the treatment-related adverse events (TRAEs) were grade 1 or 2 and were considered manageable. Grade 3/4 TRAEs consisted of anemia (14.0%), peripheral sensory neuropathy (2.3%), vomiting (2.3%), and diarrhea (2.3%). No treatment-related deaths occurred. Conclusions: Utidelone monotherapy exhibits promising antitumor activity and manageable safety profile in heavily pretreated mCRPC patients, including those who have progressed on ARPIs, abiraterone, and docetaxel. The study results support further investigation of this regimen. Clinical trial information: ChiCTR2200061635.