Avelumab (Ave) in combination with other anticancer agents as first-line maintenance (1LM) treatment for advanced urothelial carcinoma (aUC): Primary analysis from the JAVELIN Bladder Medley phase 2 trial.

Abstract

739 Background: Ave 1LM is a recommended treatment option for patients (pts) with aUC without progression after 1L platinum-based chemotherapy (PBC). In the interim analysis of the JAVELIN Bladder Medley trial (NCT05327530), 1LM with Ave + sacituzumab govitecan (SG; Trop-2–directed antibody-drug conjugate) improved progression-free survival (PFS) vs Ave monotherapy (mono), thereby meeting the study’s primary endpoint. Here, we report the primary analysis in all study arms, including Ave + SG, Ave + M6223 (anti-TIGIT), and Ave + NKTR-255 (polymer-conjugated IL-15 agonist). Methods: Pts with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L PBC were randomized 1:2:2:2 to receive Ave mono (control), Ave + SG, Ave + M6223, or Ave + NKTR-255, stratified by presence of visceral metastases. Primary endpoints were investigator-assessed PFS and safety. Per protocol, PFS and overall survival (OS) data in the Ave mono arm for each comparison were extended using propensity score–weighted data from the JAVELIN Bladder 100 phase 3 trial (NCT02603432), which was additionally down-weighted to match the number of randomized pts. Results: 256 pts were randomized. Baseline characteristics were generally similar between arms. At data cutoff (Apr 28, 2025), median follow-up for OS was ≥16.8 months in all arms. Study treatment was ongoing in the Ave + SG, Ave + M6223, Ave + NKTR-255, and Ave mono arms in 20/74 (27.0%), 17/72 (23.6%), 22/73 (30.1%), and 8/37 (21.6%) pts, respectively. In the Ave + SG, Ave + M6223, Ave + NKTR-255, and Ave mono arms, treatment-related adverse events (TRAEs) of any grade (grade ≥3) occurred in 97.3% (71.2%), 76.4% (8.3%), 95.8% (20.8%), and 66.7% (5.6%) of pts, respectively. 2 pts had a TRAE that led to death (Ave + SG and Ave + NKTR-255 arms). PFS and OS results (including extended data in the Ave mono arm) are shown in the Table. Conclusions: In the primary analysis of the JAVELIN Bladder Medley trial, Ave + SG as 1LM in pts with aUC without progression after 1L PBC showed improved PFS vs Ave mono. While OS data are still immature, OS trends favored Ave + SG, Ave + M6223, and Ave + NKTR-255 vs Ave mono. No new safety signals were identified. Follow-up for OS is ongoing. Clinical trial information: NCT05327530 . Ave + SG (n=74) Ave mono (n=74) Ave + M6223 (n=72) Ave mono (n=74) Ave + NKTR-255 (n=73) Ave mono (n=74) Median PFS (95% CI), months 11.17(7.62-17.64) 3.75(3.32-5.65) 5.42(3.78-7.43) 4.50(3.45-7.20) 5.59(3.75-12.91) 4.50(3.48-7.20) Stratified HR (95% CI) 0.54(0.36-0.81) 0.95(0.64-1.39) 0.81(0.55-1.21) Median OS (95% CI), months NE(18.37-NE) 22.05(16.92-28.78) NE(19.45-NE) 23.23(17.68-30.82) NE(19.19-NE) 23.23(17.08-30.82) Stratified HR (95% CI) 0.69(0.41-1.17) 0.75(0.44-1.27) 0.67(0.39-1.14) HR, hazard ratio; NE, not estimable.