Avelumab (PD-L1) 1L maintenance extends OS regardless of NECTIN4/HER2 RNA in la/mUC

Avelumab is an anti–PD-L1 monoclonal antibody used as first-line (1L) maintenance after platinum-based chemotherapy (PBC) in unresectable locally advanced/metastatic urothelial carcinoma (la/mUC). In the Phase 3 JAVELIN Bladder 100 trial (NCT02603432), progression-free patients after 4–6 cycles of 1L PBC with RNAseq biomarker data (n=560) were stratified by tumor NECTIN4 and HER2 (ERBB2) RNA expression (median split): OS favored avelumab + best supportive care (BSC) vs BSC alone across all combined-expression groups—high/high mOS 23.0 vs 14.3 months (HR 0.73), low/low 29.8 vs 18.8 (HR 0.78), high/low 18.4 vs 17.4 (HR 0.84), with the abstract also stating benefit by each marker alone (safety by subgroup not reported here). This is directionally consistent with the overall JAVELIN Bladder 100 SOC result (avelumab maintenance improved OS vs BSC after response/SD on 1L platinum), suggesting NECTIN4/HER2 RNA—while relevant for ADC targeting biology—doesn’t look like a practical selection biomarker for avelumab maintenance based on these exploratory splits.