Neoadjuvant nivolumab with or without visugromab in muscle-invasive bladder cancer: the phase 2a GDFATHER-NEO trial.

Neoadjuvant nivolumab plus visugromab in cisplatin-ineligible/refusing muscle-invasive bladder cancer achieved a 33% pathologic complete response versus 8% with nivolumab plus placebo.

• Why it matters: GDF-15 is overexpressed in muscle-invasive bladder cancer and may help tumors resist PD-1/PD-L1 blockade, creating a need for strategies that improve response rates.
• What they did: In the exploratory, stratified, placebo-controlled phase 2a GDFATHER-NEO trial, 31 patients received three cycles of nivolumab 480 mg 4-weekly plus visugromab 20 mg/kg 4-weekly (n=16) or placebo (n=15), then underwent radical cystectomy or repeat transurethral resection.
• The result: Major pathologic response was 60% versus 23%, radiographic overall response rate was 60% versus 15%, and responses to nivolumab plus visugromab were linked to higher baseline total and Ki-67+ CD8+ T-cell densities.