Phase II study of utidelone plus fruquintinib for the treatment of platinum-resistant recurrent ovarian cancer (FRUTD trial).

Abstract

5579 Background: Patients (pts) with platinum-resistant ovarian cancer (PROC) have a poor prognosis, and traditional cytotoxic drugs have limitations in efficacy and safety. Therefore, we are exploring the combination of utidelone capsule (UTD2), a novel oral microtubule inhibitor, with fruquintinib capsule (F), a tyrosine kinase inhibitor targeting VEGFR 1,2,3, for the treatment of platinum-resistant recurrent ovarian cancer. Methods: This study is an open-label and Simon two-stage phase II clinical trial, aiming to enroll 35 pts with platinum-resistant recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. All pts were high-grade serous ovarian cancer, with prior 1-5 lines of systemic therapy, and no more than 3 lines of subsequent therapy after platinum-resistant recurrence. Subjects received F in combination with UTD2 in 21-day cycles. The dose of F was 5 mg once daily, taken orally from day 1 to day 14 of each cycle. The dose of UTD2 was 60 mg/m²/day once daily, taken orally from day 1 to day 5 of each cycle. Primary endpoint was objective response rate (ORR) per RECIST v1.1. In Stage 1, 14 pts received per protocol treatment, and the study would proceed to Stage 2 (enrolling additional 21 patients) if ≥2 objective responses (CR/PR) were observed in Stage 1. Secondary endpoints included investigator-assessed progression-free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS) and Safety. Results: From March 18, 2025 to December 22, 2025, 19 pts were enrolled. Median age was 59 years (range, 44-68) with an ECOG PS score of 1. Median prior lines systemic therapy was 3 (range, 1-5) with 1, 2, 3, 4 and 5 lines for 4 pts (21.1%), 2 pts (10.5%), 6 pts (31.6%), 5 pts (26.3%), and 2 pts (10.5%), respectively. Median number of chemotherapy lines after platinum resistance was 1 (range, 0-3), with 0, 1, 2, or 3 lines of chemotherapy for 6 pts (31.6%), 6 pts (31.6%), 5 pts (26.3%), and 2 pts (10.5%), respectively. 14 pts were evaluated for efficacy with an outcome of 1 complete response, 8 partial responses and 5 stable diseases. ORR was 64.3% (95% CI: 38.8-83.7) and DCR was 100%. Median PFS was 7 months (95% CI: 2.8-7.2) and median OS has not reached. The Grade 3 treatment-related AE (TRAE) included neutropenia (n=2), mucositis oral (n=1), palmar-plantar erythrodysesthesia syndrome (n=1), skin ulceration (n=1), diarrhea (n=1), pain (n=1) and neurotoxicity (n=1). There were no ≥Grade 4 TRAE. 1 patient discontinued UTD2+F due to TRAEs. Conclusions: Utidelone plus Fruquintinib demonstrated encouraging efficacy for the treatment of PROC with a tolerable safety profile. This study is still actively ongoing, and further data will be provided at time of presentation. Clinical trial information: NCT06973421 .