Summary
In the 31-patient exploratory GDFATHER-NEO trial, nivolumab plus visugromab was associated with higher pathological and radiographic response rates than nivolumab plus placebo before bladder surgery. The small, nonrandomized study was not designed to establish long-term benefit.
An exploratory phase 2a trial published in Nature Medicine on 24 October 2026 reported higher pathological and radiographic response rates when the investigational antibody visugromab was added to nivolumab before surgery for muscle-invasive bladder cancer. The GDFATHER-NEO trial enrolled 31 people with newly diagnosed disease who were ineligible for, or declined, cisplatin-based chemotherapy.
Visugromab is designed to neutralise growth differentiation factor-15 (GDF-15), a protein implicated in suppressing immune activity in tumours. Nivolumab blocks PD-1, an immune checkpoint that can limit T-cell activity. The trial tested whether targeting both pathways could improve response to treatment before surgery.
How the trial was conducted
Participants had clinical stage T2–T4a, N0M0 bladder cancer and were assigned to three four-weekly cycles of nivolumab, either with visugromab or with placebo. Nivolumab was given at 480 mg; visugromab was given at 20 mg per kilogram. Patients were stratified by tumour stage and PD-L1 expression, then allocated sequentially within those groups. This was not a randomised trial: patients were blinded to their assignment, but investigators and sponsor staff were aware of it.
The main outcomes included pathological complete response (pCR), meaning no residual viable tumour in the post-treatment specimen, and radiographic response assessed using RECIST version 1.1. Of the 31 enrolled participants, 28 were evaluable for each locally assessed response outcome.
Response rates and safety
Among evaluable patients, local pathology assessment found a pCR in 5 of 15 patients (33%; 95% confidence interval (CI) 12–62%) given nivolumab plus visugromab, compared with 1 of 13 (8%; 95% CI 0–36%) given nivolumab plus placebo. Major pathological response rates were 60% and 23%, respectively. Local imaging assessment recorded an overall response in 9 of 15 patients (60%; 95% CI 32–84%) in the combination group and 2 of 13 (15%; 95% CI 2–45%) in the placebo group. Central pathology review also favoured the combination, reporting pCR rates of 47% versus 17% among evaluable patients.
Grade 3–4 treatment-related adverse events occurred in 2 of 16 patients (13%) receiving nivolumab plus visugromab and 3 of 15 (20%) receiving nivolumab plus placebo. No patient in the combination group discontinued treatment because of a treatment-related adverse event, and no surgery delay was attributed to neoadjuvant treatment.
What the results can tell us
The response differences provide an early clinical signal for combining GDF-15 neutralisation with PD-1 blockade in this setting. The researchers also found that, among patients receiving the combination, response was associated with higher baseline densities of CD8+ T cells, including proliferating CD8+ cells. This exploratory finding may help guide further study of which tumours are more likely to respond.
The trial was small and was not powered for a formal comparison between groups; its response estimates are descriptive. Sequential allocation rather than randomisation also leaves the comparison open to possible selection or period effects. Median follow-up was 15.7 months, with six event-free survival events recorded and median event-free survival not reached in either group. The results therefore do not yet establish whether the higher response rates translate into longer-term disease control or safe bladder preservation. Larger randomised trials with longer follow-up are needed to assess those outcomes.