A novel oral microtubule inhibitor utidelone capsule (UTD2): A phase 1 clinical study to assess the tolerability, safety, and efficacy in advanced solid tumors.

e15014 Background: Utidelone is a potential best-in-class novel microtubule stabilizing agent that offers several advantages including improved efficacy and safety, broader anti-cancer spectrum, blood-brain barrier penetrance, and response against multidrug-resistant tumors. Utidelone injection (UTD1) has been approved for advanced breast cancer in China since 2021 (30 mg/m 2 /d-5day in combination with capecitabine; 35mg/m 2 /d-5day for monotherapy’s recommended dose). Utidelone is not susceptible to P-glycoprotein, leading to better oral bioavailability and successful development of an oral capsule. This is the first-in-human study of Utidelone Capsule (UTD2) in the United States. Methods: This is an ongoing phase I, open-label, dose escalation study (NCT05681000). Eligible patients are aged ≥18, and have an ECOG PS of 0-1, life expectancy ≥12weeks, adequate organ functions, pathologic confirmed advanced solid tumor refractory to prior standard therapies. Patients are treated with UTD2 monotherapy. The starting dose is 25 mg/m 2 /d-5day, with planned escalation to 50, 75, 100 mg/m 2 /d-5day, 70 mg/m 2 /d-7day and 85 mg/m 2 /d-7day in a 21-day cycle. The primary objective is to determine DLT and MTD. Secondary objectives include efficacy, pharmacokinetic profile and phase II dose recommendation. Results: As of 22 nd January 2024, 10 advanced solid tumor patients were enrolled with median age of 62.5 years (range 52.0-81.0), 5 females and 5 males. All patients had received prior treatment in advanced settings. Dose escalation is ongoing, and 100mg/m 2 /d-5day cohort is under evaluation. The first 8 patients were evaluated for efficacy with an outcome of 1 CR (ovarian cancer), 5 SD (prostate adenocarcinoma, testicular Sertoli cell tumor, non-small cell lung cancer, pancreatic adenocarcinoma and appendiceal adenocarcinoma) and 2 PD (carcinoma of fallopian tube and adenocarcinoma of sigmoid colon), among whom 5 patients are still on the treatment with durations of 2 to 11 cycles. The ovarian patient with CR was enrolled to the lowest dose cohort, and is still on treatment. She is heavily pre-treated with multiple prior lines including chemotherapies. Regarding safety, most treatment-emergent adverse events (TEAEs) were Grade 1/2, manageable, and included diarrhoea, nausea, alopecia. There were two cases of Grade 3 diarrhea that recovered to Grade 1 through dose reduction or medical support. No grade 4 or 5 adverse events and no treatment discontinuations due to AE were reported. There have been no DLTs and the MTD is not yet reached. Conclusions: This study has demonstrated encouraging anti-tumor activity with good tolerance and manageable safety profile of UTD2 in patients with heavily pre-treated advanced solid tumors. This study is still actively ongoing, and further data will be provided at time of presentation. Clinical trial information: NCT05681000 .