Ave + SG (TROP2 ADC) extends PFS across visceral/liver/bone subgroups vs avelumab alone in 1L maintenance aUC

Avelumab is a PD-L1 inhibitor, and sacituzumab govitecan (SG) is a TROP2-directed ADC delivering SN-38; this randomized Phase 2 JAVELIN Bladder Medley trial (NCT05327530) tested Ave + SG vs avelumab monotherapy as 1L maintenance in unresectable/metastatic urothelial carcinoma without progression after 4–6 cycles of platinum chemo (n=111; 74 vs 37; randomized 2:1; stratified by visceral metastases at start of chemo). At the Apr 28, 2025 cutoff (median PFS follow-up 15.7 vs 25.1 months), PFS favored Ave + SG in every metastatic-site subgroup reported: visceral 9.03 vs 2.20 months (HR 0.49), nonvisceral 14.69 vs 7.33 (HR 0.61), bone 9.26 vs 2.33 (HR 0.40), lung 8.77 vs 1.81 (HR 0.43), liver 8.77 vs 2.69 (HR 0.48), lymph node–only 14.00 vs 7.59 (HR 0.65); OS was immature, and the control arm’s visceral/nonvisceral estimates were extended using propensity score–weighted JAVELIN Bladder 100 data per protocol. Toxicity was the clear tradeoff: grade ≥3 TRAEs were 57.9%–82.4% with Ave + SG across metastatic-site subgroups vs 0%–9.1% with avelumab alone; for context, SOC 1L maintenance avelumab (vs best supportive care) improved OS to 23.8 vs 15.0 months (HR 0.76) in JAVELIN Bladder 100, but did not carry the same high grade ≥3 AE burden seen with adding SG here.