Avelumab + sacituzumab govitecan (SG) vs avelumab monotherapy as first-line (1L) maintenance treatment in patients (pts) with advanced urothelial carcinoma (aUC): Interim analysis from the JAVELIN Bladder Medley phase 2 trial.

4501 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in pts with aUC without progression following 1L platinum-based chemotherapy (PBC). The JAVELIN Bladder Medley phase 2 trial is investigating the combination of avelumab with other antitumor agents in this pt population to assess efficacy and safety vs avelumab maintenance monotherapy. SG is a Trop-2–directed antibody and topoisomerase inhibitor drug conjugate being investigated in solid tumors. Here we report an interim analysis of avelumab + SG vs avelumab monotherapy. Methods: Eligible pts had unresectable locally advanced or metastatic UC, ECOG performance status (PS) 0-1, and no disease progression after 4-6 cycles of 1L PBC. Pts were randomized 2:1 to avelumab + SG or avelumab monotherapy, stratified by presence of visceral metastases at start of 1L PBC. Primary endpoints were investigator-assessed PFS and safety; OS was a secondary endpoint. For PFS and OS analyses, data in the avelumab monotherapy arm were extended per protocol using propensity score-weighted JAVELIN Bladder 100 data. Results: At data cutoff (Sep 16, 2024), 38 of 74 pts (51.4%) in the avelumab + SG arm and 10 of 37 pts (27.0%) in the avelumab monotherapy arm were still receiving study treatment. In the avelumab + SG and avelumab monotherapy arms, respectively, median age was 70 and 67 years, 50.0% and 51.4% had visceral metastases at start of 1L PBC, and a lower proportion of pts in the avelumab + SG arm had ECOG PS of 1 (31.1% vs 54.1%). Median PFS was 11.17 months (95% CI, 7.43-not estimable [NE]) with avelumab + SG vs 3.75 months (95% CI, 3.32-6.77) with avelumab monotherapy (hazard ratio [HR], 0.49 [95% CI, 0.31-0.76]). OS data were immature at cutoff; median OS was not reached (95% CI, 15.51-NE) in the avelumab + SG arm vs 23.75 months (95% CI, 18.79-30.82) in the avelumab monotherapy arm (HR, 0.79 [95% CI, 0.42-1.50]). In the avelumab + SG and avelumab monotherapy arms, respectively, treatment-related adverse events (TRAEs) of any grade occurred in 71 (97.3%) vs 23 pts (63.9%), and were grade ≥3 in 51 (69.9%) vs 0 pts. TRAEs led to discontinuation of both avelumab + SG in 4.1% (SG only in 12.3%) vs avelumab monotherapy in 2.8%. One pt in the avelumab + SG arm had a SG-related AE that led to death (acute subarachnoid hemorrhage in the setting of sepsis and pancytopenia). Conclusions: In pts with aUC without progression after 1L PBC, avelumab + SG as maintenance treatment improved PFS vs avelumab monotherapy. TRAEs were more frequent in the combination arm and were consistent with the known safety profile of SG and avelumab. Further investigation of avelumab in combination with anti–Trop-2 antibody-drug conjugates in aUC is warranted. Clinical trial information: NCT05327530 .