Effcacy and safety results of a multi-center phase I/II study of utidelone capsule, a novel oral microtubule inhibitor.

e13110 Background: Utidelone is a best-in-class novel microtubule inhibitor that offers several advantages including improved efficacy and safety, broader anti-cancer spectrum, and response against multidrug-resistant tumors. Utidelone injection (UTD1) has been approved for advanced breast cancer (BC) in China. Attempts to develop oral microtubule inhibitors have not made significant progress. No oral microtubule inhibitors have been approved in the United States. This is the first clinical study to investigate utidelone oral formulation, i.e. utidelone capsule (UTD2) in China. Methods: Phase I includes dose escalation and bioavailability in advanced solid tumor patients. For dose escalation, patients are treated with UTD2 monotherapy at starting dose of 50 mg/m 2 /d-5day (2 patients), with escalation to 75 mg/m 2 /d-5day and 75 mg/m 2 /d-7day (3 patients for each) in a 21-day cycle. For bioavailability study, 20 patients are randomly assigned to one of the crossover groups in a 1:1 ratio. Group A received UTD2 at 60 mg/m 2 /d orally under fasting state; Group B received UTD1 iv at 30 mg/m 2 /d, followed by crossed over after 7-day washout interval by dosing daily for 5 days. Patients in both groups then received UTD2 orally after a high-fat meal on Day 29. Phase II is for UTD2 at 60mg/m 2 /d-5day in combination with capecitabine at 1000mg/m 2 bid-14day in a 21-day cycle for metastatic BC, with ORR as the primary objective. Results: As of 6 th January 2025, the completed phase I showed no patient experienced DLT and the most common ≥ Grade 3 AE was diarrhea appeared at 75 mg/m 2 /d-7day, but recovered within 24 hours after supportive treatment. 75 mg/m 2 /d-5day was recommended as monotherapy dose. 6 patients were evaluable for efficacy with 3 PR (1 for each for cohort) and 3 SD, with DoT of 2-13 cycles. Most TEAEs were Grade 1/2, no AEs lead to death or termination from study. The AUC inf of 30 mg/m 2 UTD1 and 60 mg/m 2 UTD2 was 3119.708 h*ng/mL and 2188.184 h*ng/mL, respectively, demonstrating a bioavailability F% of 35.1%. The C max and AUC 0-t of postprandial UTD2 was reduced by 72.7% and 23.5%, respectively, compared with fasting UTD2. For phase II, 31 advanced BC patients were enrolled, 26 patients are still under treatments. 21 patients were evaluated for efficacy with 9 PR and 10 SD. The ORR was greater than 42.1% (CBR was 90.5%) . Results were consistent with UTD1 phase III (49.8% ORR, 65.8% CBR, orall ASCO 2018). The most common TEAEs included diarrhoea with 6 ≥ Grade 3 (19.4%), and neutropenia with 3 ≥ Grade 3 (9.7%) which recovered with supportive treatment. There were 2 SAEs including Grade 3 diarrhoea and Grade 4 neutropenia. Conclusions: This study demonstrated UTD2’s good bioavailability as a microtubule inhibitor, manageable safety, and promising combination therapy efficacy consistent with the injectable formulation for the treatment of advanced BC. The final data will be provided at the time of presentation. Clinical trial information: NCT05700084 .