GDF-15 blocker boosts nivolumab effect in MIBC
Adding the growth differentiation factor 15 (GDF-15) inhibitor visugromab to PD-1 blockade may improve outcomes for patients with anti-PD-1–naive muscle-invasive bladder cancer (MIBC) who are unable or unwilling to undergo neoadjuvant chemotherapy, report the GDFATHER-NEO trial investigators.
The combination tested in this phase 2 trial was three times more efficacious than nivolumab monotherapy, Andrea Necchi (Vita-Salute San Raffaele University, Milan, Italy) told delegates at the European Society of Medical Oncology (ESMO) Congress 2025 in Berlin, Germany.
The 31 trial participants had newly diagnosed T2-4a, N0, M0 MIBC. A third were considered unfit for neoadjuvant chemotherapy, but two-thirds had refused it.
After three treatment cycles, the pathologic complete response (pCR) rate in 29 evaluable patients was 33.3% for those who received nivolumab 480 mg plus visugromab 20 mg/kg every 4 weeks, compared with 7.1% for those given nivolumab plus placebo. The corresponding major pathologic response rates were 66.7% versus 21.4%.
In line with this, more patients in the combination group received bladder-sparing surgery, at 40.0% versus 21.5% of those in the monotherapy group.
At randomization, trial participants were stratified by a PD-L1 combined positive score of 10%, and Necchi highlighted that those with a score of 10% or higher were most likely to achieve pCR with the addition of visugromab.
Moreover, nivolumab plus visugromab was “overall a pretty well-tolerated combination,” said Necchi.
In the full safety population, 19.4% of patients had a grade 3 treatment-related adverse event (TRAE), including two cases of elevated liver enzymes in each treatment group and one case of hypothyroidism in the nivolumab placebo group. Two TRAEs led to discontinuation, both in the visugromab group – one instance of increased liver enzymes and one of myalgias plus arthralgia.
The combination of visugromab and nivolumab “certainly warrants further investigation in much larger studies and maybe in different settings,” Necchi concluded, stressing that GDFATHER-NEO was a proof-of-concept study with a small sample size.
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