A phase 2, open-label, randomized study of livmoniplimab in combination with budigalimab versus chemotherapy in patients with metastatic urothelial carcinoma.

• DOI: 10.1200/jco.2025.43.16_suppl.tps4618
• Publication Date: 2025-05-28T14:23:48Z
• Authors: Terence W. Friedl...; J. Thaddeus Beck; Eli Rosenbaum; Avivit Peer; Shingo Hatakeyama; Nadine Jahchan; Cathy Zhou; Cristiano Ferlini; Sujata Jha; Duyen Andrina Ngo; Matthew D. Galsky
• Keywords: Metastatic Urothelial Carcinoma; Urothelial cancer; Open label

TPS4618 Background: Urothelial carcinoma (UC) has a high mortality rate in patients (pts) with metastatic disease. While immune checkpoint inhibitors (CPI), including programmed cell death protein 1 (PD-1) combined chemotherapy (CTx) or enfortumab vedotin (EV), have been approved for first-line treatment of (m)UC, many pts de novo develop acquired resistance. For without response to frontline whose disease progressed on prior CPI combinations, optimal is unclear and new therapies are urgently needed. Glycoprotein A repetitions predominant (GARP) membrane-bound receptor that complexes latent transforming growth factor (TGF)-β1; the release active TGF-β1 from this complex suppresses antitumor responses. Livmoniplimab (livmo), an antibody targeting GARP:TGF-β1 complex, prevents TGF-β1, thereby promoting activity. first-in-human phase study (NCT03821935) demonstrated combining livmo anti–PD-1 mAb budigalimab (budi) resulted manageable safety profile promising activity PD-1–refractory advanced UC (J Clin Oncol 2024;42[suppl 4]: abs 617). Herein, we describe 2 evaluating + budi vs CTx mUC (NCT06632951). Methods: This multicenter, open-label, randomized enrolling aged ≥18 years who mUC, measurable per RECIST v1.1, ECOG PS 0–1, experienced progression ligand therapy. Platinum (Pt)-eligible must received Pt-containing regimen; can receive EV on/after receiving treatment. Primary objectives identify recommended 3 dose combination evaluate overall survival. Secondary include progression-free survival, best complete partial response, duration assessment tolerability, pharmacokinetics, immunogenicity combination. Pts will be 1:1:1 arms: 1) Q3W Q3W; 2) 3) investigator’s choice (paclitaxel, docetaxel, gemcitabine). stratified by (0 therapy (pembrolizumab CTx). Treatment Arms continue until maximum 35 cycles. Arm 3, consistent local guidelines/practice pt population. No crossover between arms permitted. all pts, discontinued at if other protocol-defined discontinuation criteria met. In total, approximately 150 (50 pts/arm) planned enrollment globally. Clinical trial information: NCT06632951 .