Final results of a phase II study of utidelone capsule, the first solid oral microtubule stabilizer, in metastatic breast cancer patients.

1105 Background: Attempts to develop oral microtubule inhibitors have not made significant progress in decades. Utidelone is a novel microtubule inhibitor insusceptible to P-glycoprotein, enabling higher oral bioavailability and response against multidrug-resistant tumors. Utidelone injection (UTD1) has been approved for metastatic breast cancer (mBC) in China in 2021; utidelone capsule (UTD2) is the first solid oral formulation of microtubule stabilizer in clinical stage globally. Our previous phase I study of UTD2 showed promising activity with no DLTs being observed in late line metastatic solid tumors, and 75 mg/m 2 /d*5 was recommended as monotherapy dose (ASCO 2025). PopPK analysis indicated that AUC of UTD2 of 75 mg/m 2 /d reached 80%-125% of the AUC of UTD1. The absolute bioavailability of UTD2 vs. UTD1 was 35.1%. Here we report the final results of a phase II study of UTD2 in combination with capecitabine (CAP) in mBC. Methods: This is a single-arm, multi-center phase II trial. The key inclusion criteria included patients with metastatic breast cancer, refractory to anthracycline or taxane treatment, ≤ 4 lines of prior chemotherapy, ECOG score of 0-1 and an expected survival of ≥ 12 weeks. Eligible patients received UTD2 at 60mg/m 2 /d*5 in combination with CAP at 1000mg/m 2 bid*14 in a 21-day cycle. The primary endpoint was ORR; the secondary endpoints included PFS and safety. Results: By data cutoff on October 8, 2025, the recruitment had been completed. 50 mBC pts were enrolled with 72% of HR+/HER2-, 24% of TNBC, and 2% of HR+/HER2+. Twenty-one (21) pts (42%) had received ≥3 lines of treatment. 100% of the patients had received taxane or anthracycline and 86% had visceral metastases. Forty-four (44) pts were evaluated for efficacy with the best responses of 27 PR and 12 SD. The confirmed ORR was 52.3% (95%CI 36.7, 67.5) and DCR was 88.6% (95%CI 75.4, 96.2). Median PFS was 8.25 (95%CI 5.36, 10.58) months and median DoR was 7.62 months (95%CI 4.17, NE) (median treatment cycles was 9.0), demonstrating better efficacy than UTD1 +CAP (ORR 40.4%, CBR 53.9%, PFS 7.72 months, Lancet Oncol 2017) in mBC pts. The most prominent ≥ Grade 3 TEAEs was diarrhea (28%). However, the incidence of peripheral neuropathy (PN) was significantly decreased compared with UTD1+CAP (Grade 3 PN only 2% vs 25.1%) while maintaining the characteristic of low hematological toxicity (only 10% for both ≥ Grade 3 Neutropenia and Leukopenia). Treatment related discontinuations occurred in only 2 pts (4%). Conclusions: This study demonstrated excellent efficacy of UTD2+CAP in mBC pts. The safety profile with significantly decreased PN and low hematological toxicity highlighted another advantage of this regimen. Utidelone capsule is anticipated to dramatically improve medication convenience and enhance patient compliance. Clinical trial information: NCT05700084 .