ESMO Congress 2026

Visugromab (CTL-002) is a monoclonal antibody that neutralizes GDF-15, and its therapeutic logic rests on the following chain of evidence: GDF-15 is abundantly produced by many cancer types and interferes with antitumor immunity, and in preclinical models GDF-15 blockade synergized with anti-PD-1 ^[1]; in NSCLC, investigators have retrospectively evaluated the association between tumor-tissue GDF-15 expression levels and outcomes (PFS, OS) on nivolumab ^[2]; the roles of GDF15 in immune evasion, metastasis, and therapy resistance have also been described across multiple tumor types including head and neck squamous cell carcinoma ^[3]. On the clinical side, this class has no phase 3 data; the evidence that stands is the phase 1/2a GDFATHER-1/2a trial (NCT04725474) in anti-PD-1/PD-L1 refractory advanced solid tumors, which showed durable and deep responses in non-squamous NSCLC and urothelial cancer ^[1]; the long-term follow-up published in 2026 further showed ORRs of 18.2% (4/22) in heavily pretreated nsq NSCLC, 18.5% (5/27) in UC, and 14.3% (4/28) in HCC expansion cohorts, with median duration of response reaching 32.2 months ^[5].

At ESMO26, Andrea Necchi presented GDFatherNeo: moving visugromab + nivolumab (N+V) from the refractory setting into neoadjuvant treatment of muscle-invasive bladder cancer (MIBC). The on-site figures can only be quoted as given: pCR rate of 33% versus 8% for nivolumab + placebo; at median follow-up of 15.7 months, all pCR patients remained event-free; only 1 relapse event occurred among major responders in the N+V arm (a pTa relapse); 4/5 pCR patients in the N+V arm skipped radical cystectomy (RC). Safety was quite good, and Choueiri likewise confirmed no new safety signal. On biomarkers, pre-existing CD8+ infiltration was associated with response to N+V. The results were published simultaneously in Nature Medicine, and the author highlighted the academic-industry collaboration behind the trial.

Relative to prior knowledge, this readout advances three things. First, the population moves from anti-PD-1/PD-L1 relapsed/refractory, heavily pretreated advanced solid tumors ^[1][5] to a neoadjuvant, potentially curative bladder cancer setting, with bladder preservation (4/5 pCR skipping RC) entering the picture. Second, whereas earlier efficacy evidence came from phase 1/2a exploration, this time there is a direct comparison against nivolumab + placebo (33% vs 8%), and it further consolidates the urothelial direction - one of the entities identified in the GDFATHER trial as frequently immunosuppressed by GDF-15 ^[1]. Third, on biomarkers, earlier work centered on the relationship between tumor GDF-15 expression and immunotherapy outcomes ^[2], while this readout indicates that baseline CD8+ infiltration is likewise associated with response.

The limitations are straightforward: the posts disclose no sample size, trial phase, or statistical design, and absolute numbers such as 5 pCR patients and 4/5 skipping RC are small; a median follow-up of 15.7 months remains short for judging event-free survival and bladder-preservation outcomes, and the exact population and dosing should be confirmed in the simultaneously published Nature Medicine paper.