At the ESMO Congress 2025, results from the GDFather-NEO trial (NCT06059547) were presented, evaluating the novel GDF-15 inhibitor visugromab (20 mg/kg) in combination with nivolumab (480 mg) compared to nivolumab plus placebo in patients with muscle-invasive bladder cancer (MIBC) who were cisplatin-ineligible or declined chemotherapy.
This multicenter phase II study enrolled 31 patients, with 28 evaluable for efficacy. The visugromab plus nivolumab (N/V) arm achieved markedly higher efficacy compared to nivolumab plus placebo (N/P), including:
Pathologic complete response (pCR): 33.3% vs. 7.7%
Major pathologic response (MPR): 66.7% vs. 23.1%
Objective response rate (ORR, RECIST v1.1): 60% (7 CR, 2 PR) vs. 15.4% (0 CR, 2 PR)
The benefit of N/V was consistent across all tumor stages and most pronounced in patients with PD-L1 CPS ≥10%. Importantly, the combination showed excellent tolerability, with safety data confirming good management and no unexpected toxicities.
Baseline GDF-15 serum levels were comparable between treatment arms, and translational data supported GDF-15 blockade as a mechanism to overcome immune resistance to PD-(L)1 inhibition.
These findings demonstrate that visugromab plus nivolumab tripled the response rate compared with nivolumab alone, positioning GDF-15 blockade as a promising new strategy in neoadjuvant MIBC therapy. Further trials are warranted to confirm efficacy and explore tumor response–guided bladder preservation approaches.
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