A phase III randomized trial of eribulin (E) with gemcitabine vs standard of care (SOC) for patients (pts) with metastatic urothelial carcinoma (mUC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937—Updated design.

TPS887 Background: UC is the 2nd most common genitourinary cancer. Enfortumab vedotin (EV) + pembrolizumab became a SOC in 2023 in frontline mUC setting. There is not established standard of care for the subsequent lines of therapy limiting treatment options to platinum-based chemotherapy, docetaxel, paclitaxel, gemcitabine, or Sacituzumab govitecan monotherapy. Erdafitinib remains an option for pts with FGFR3 alterations. A phase I/II CTEP study of eribulin (E) for mUC established the activity of E with an objective response rate (ORR) of 37.5%, median progression-free survival (PFS) of 4.1 months (mo), and median overall survival (OS) of 9.5 mo (N=150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed an ORR of 50%, median OS of 11.9 mo, and median PFS of 5.3 mo (N=24). The most common Grade 3-4 toxicities included neutropenia (63%), anemia and fatigue (29% each). Pts with liver metastases benefited from therapy with an ORR of 71% (n=7) for GE vs. 24% for E (N=49). This trial has now been amended to account for first-line treatment changes and to include SG as a control arm option. In this amendment the eribulin alone arm was closed to simplify the design and reduce the sample size. Methods: This is an updated phase III, randomized trial comparing GE vs. SOC (SG, docetaxel, paclitaxel, or gemcitabine monotherapy). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle. Gemcitabine is added to E at 1000 mg/m2 on D 1 and D 8. SOC follows approved dosing. There is no limit to the number/sequence of prior regimens. All pts must have: received systemic therapy with EV; received PD1/PDL1 Ab or be deemed ineligible for PD1/PDL1 Ab. The study seeks to find at least a 50% increase in the primary endpoint of OS (Hazard Ratio (HR) = 0.667). Secondary endpoints include ORR and PFS. This design has a power of 80% and a one-sided alpha of 0.05 to detect a HR=0.667. We require 92 pts in each arm for a total of 168 eligible pts. The amended and restructured study was approved in January of 2024. Funding: National Institutes of Health/National Cancer Institute grants U10CA180888, U10CA180819. Eribulin is provided by Eisai. Clinical trial information: NCT04579224 .