Avelumab + sacituzumab govitecan (Ave + SG) vs avelumab monotherapy (Ave mono) as first-line (1L) maintenance treatment for advanced urothelial carcinoma (aUC): Updated subgroup analyses of JAVELIN Bladder Medley based on metastatic sites.

4568 Background: Ave 1L maintenance is a recommended treatment option for patients (pts) with aUC without progression after 1L platinum-based chemotherapy (PBC). In the JAVELIN Bladder Medley phase 2 trial (NCT05327530), 1L maintenance with Ave + SG (Trop-2–directed antibody-drug conjugate) improved progression-free survival (PFS) vs Ave mono (primary endpoint). In pts with aUC, presence of visceral metastases (including liver or lung) is associated with poorer prognosis. We report updated subgroup analyses from the primary analysis of JAVELIN Bladder Medley based on metastatic site. Methods: Pts with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L PBC were randomized 2:1 to receive Ave + SG or Ave mono, stratified by presence of visceral metastases at start of 1L PBC. Primary endpoints were investigator-assessed PFS (measured from randomization) and safety; overall survival (OS) was a secondary endpoint. For visceral and nonvisceral subgroups, PFS and OS data in the Ave mono arm were extended per protocol using propensity score–weighted data from the JAVELIN Bladder 100 phase 3 trial; extended data were not available for other subgroups. Results: At the start of 1L PBC, of 74 and 37 pts in the Ave + SG and Ave mono arms, respectively, 37 (50.0%) and 19 (51.4%) had visceral metastases, 20 (27.0%) and 11 (29.7%) had lung metastases, 17 (23.0%) and 7 (18.9%) had liver metastases, 17 (23.0%) and 11 (29.7%) had bone metastases, and 26 (35.1%) and 11 (29.7%) had lymph node–only disease. At data cutoff (Apr 28, 2025), in the Ave + SG and Ave mono arms, respectively, median follow-up for PFS was 15.7 and 25.1 mo. Across all subgroups, PFS was prolonged with Ave + SG vs Ave mono (Table); OS analyses were immature. In the Ave + SG and Ave mono arms, respectively, grade ≥3 treatment-related adverse events occurred in 72.2% and 5.6% of pts with visceral metastases, 57.9% and 0% of pts with lung metastases, 82.4% and 0% of pts with liver metastases, 82.4% and 0% of pts with bone metastases, 70.3% and 5.6% of pts with nonvisceral metastases, and 76.9% and 9.1% of pts with lymph node–only metastases. Conclusions: In the primary analysis of JAVELIN Bladder Medley, Ave + SG as 1L maintenance improved PFS vs Ave mono, irrespective of metastatic site. Clinical trial information: NCT05327530 . PFS, median (95% CI), mo Ave + SG Ave mono HR (95% CI) Site of metastases at start of 1L PBC Visceral* 9.03 (5.62-13.80) 2.20 (1.91-3.71) 0.49 (0.28-0.84) Nonvisceral 14.69 (7.43-NE) 7.33 (4.21-11.10) 0.61 (0.33-1.13) Lung 8.77 (4.17-9.46) 1.81 (0.07-9.26) 0.43 (0.17-1.09) Liver 8.77 (5.55-9.36) 2.69 (1.91-NE) 0.48 (0.17-1.32) Bone 9.26 (5.49-17.64) 2.33 (0.07-5.45) 0.40 (0.16-0.99) Lymph node only 14.00 (7.43-NE) 7.59 (1.87-NE) 0.65 (0.26-1.66) *Pts could have ≥1 site of visceral metastases.HR, hazard ratio; NE, not estimable.