Trial Data Show Efficacy, Tolerability of Nivolumab Plus Visogromab in MIBC

Nivolumab (Opdivo) plus visugromab showed superior efficacy to placebo and good tolerability in patients with newly diagnosed muscle-invasive bladder cancer (MIBC), according to primary trial results announced at the 2025 European Society for Medical Oncology (ESMO) Congress on October 17, 2025 in Berlin, Germany. Results of the trial were announced by Andrea Necchi, MD, Università Vita-Salute San Raffaele.¹

The GDFATHER-NEO trial (NCT06059547) is a phase 2 biomarker-oriented trial in patients with MIBC. The primary end points were pathologic complete response (pCR) and radiologic response.

There were a total of 31 patients enrolled in the trial, with 15 receiving nivolumab plus placebo, and 16 receiving nivolumab plus visugromab. The median age of patients was 76 years (range, 42–83). Patients had an ECOG score of 0 or 1. Patients received nivolumab plus placebo or nivolumab plus visugromab, administered 3 cycles every 4 weeks.

Of the total number of patients, 29 were efficacy-evaluable for histopathologic response. In the nivolumab plus placebo arm, 1 of 14 patients achieved pCR, and 2 of 14 achieved major pathologic response (MPR). In the nivolumab plus visugromab arm, 5 of 15 patients achieved pCR and MPR.

“Nivolumab in combination with visugromab showed higher efficacy with respect to histopathologic response,” Necchi said during the presentation.

As for radiologic response, 2 patients in the nivolumab plus placebo arm achieved partial response (PR); in the nivolumab plus visugromab arm, 2 patients achieved PR and 7 patients achieved complete response.

Preliminary safety data showed that any-grade treatment-related adverse events (AEs) occurred in 71% of patients (n = 22). The most common any-grade AEs across the total number of patients were asthenia (19.4%), ALT increase (12.9%), hypothyroidism (12.9%), and AST increase (9.7%). In the nivolumab plus placebo arm, any-grade AEs occurred in 60% (n = 9) of patients, and 81.3% (n = 13) in the nivolumab plus visugromab arm.

Grade 3 AEs occurred in 19.4% of patients (n = 6). Grade 3 AEs occurred in 26.7% (n = 4) of patients receiving nivolumab plus placebo, and 12.5% (n = 2) of patients receiving nivolumab plus visugromab. Serious AEs occurred in 9.7% (n = 3) of patients, and AEs leading to discontinuation occurred in 6.5% (n = 2) of patients, both in the nivolumab plus placebo arm.

“The combination of nivolumab with visugromab showed good tolerability, with no apparent increase in toxicity versus the safety profile expected for checkpoint inhibitor monotherapy,” Necchi concluded in the presentation. “Definitive safety assessment will only be possible after database lock and will require larger sample sizes in future trials.”

A phase 2 trial (NCT07098988)² is currently recruiting patients with newly diagnosed metastatic non-squamous non–small cell lung cancer to investigate visugromab plus immunochemotherapy. This trial is sponsored by CatalYm GmbH, the same company sponsoring the GDFATHER-NEO trial.

DISCLOSURES: Andrea Necchi declared financial interests with Astellas, Astra Zeneca, Bicycle Therapeutics, Bristol-Myers Squibb, Catalym, Daiichi Sankyo, Genenta Sciences, Gilead Sciences, Incyte, Johnson & Johnson, Journal of Clinical Oncology, Merck, and Samsung Bioepis.

REFERENCES

1.Necchi A, Mercinelli C, Maiorano B, et al. A blinded, exploratory phase 2 trial of nivolumab and the GDF-15 neutralizing antibody visogromab or placebo as neoadjuvant treatment of patients with muscle-invasive bladder cancer (MIBC): Primary results of the GDFATHER-NEO trial. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA110.

2.Trial investigating visogromab in combination with immunochemotherapy in 1L treatment of participants with metastatic NSCLC. ClinicalTrials.gov. Updated September 8, 2025. Accessed November 5, 2025. https://clinicaltrials.gov/study/NCT07098988