MUNICH, Germany, and SAN FRANCISCO, USA — October 24, 2026
CatalYm announced final results from its randomized Phase 2 GDFATHER-NEO trial, evaluating visugromab in combination with the PD-1 inhibitor nivolumab in patients with newly diagnosed, non-metastatic muscle-invasive bladder cancer (MIBC). Presented at the 2026 European Society for Medical Oncology (ESMO) Congress and simultaneously published in Nature Medicine, the findings showed higher response rates with visugromab plus nivolumab than with nivolumab alone. The combination achieved a pathologic complete response (pCR) rate of 33%, compared with 8% in the nivolumab-plus-placebo group. The major pathologic response (MPR) rate was 60% versus 23%, while the radiographic objective response rate (ORR) was 60% versus 15%. The study focused on patients who were ineligible for cisplatin-based chemotherapy or declined it, a population with a need for additional treatment options. Investigators also reported that a greater proportion of patients receiving the combination underwent bladder-sparing repeat transurethral resection of bladder tumor (re-TURBT) rather than radical cystectomy. Independent central review was largely consistent with local response assessments, supporting the reported findings. The combination was generally well tolerated, with no treatment-related discontinuations or new safety signals reported. These Phase 2 results support further evaluation of GDF-15 inhibition alongside checkpoint blockade, although the small study population and limited follow-up mean that larger trials are needed to confirm clinical benefit and long-term outcomes.
Visugromab Targets GDF-15 to Enhance Antitumor Immunity
Visugromab is an investigational humanized monoclonal antibody designed to neutralize growth differentiation factor-15 (GDF-15), a cytokine associated with tumor-related immune suppression and resistance to immunotherapy. GDF-15 can contribute to an environment that limits effective antitumor immune responses. CatalYm is developing visugromab to counteract this mechanism and potentially improve the activity of immune checkpoint inhibitors. In the GDFATHER-NEO study (NCT06059547), researchers evaluated visugromab plus nivolumab against nivolumab plus placebo as neoadjuvant treatment before surgery or a bladder-sparing procedure. The multicenter, stratified, single-blind Phase 2 trial enrolled 31 patients, with a median age of 76 years. Patients received three treatment cycles at four-week intervals before imaging-based restaging and subsequent radical cystectomy or re-TURBT, generally performed four to eight weeks after the final dose. At the July 15, 2026, data cutoff, 15 patients in the visugromab combination arm and 13 in the control arm were evaluable for local pathologic and radiographic primary endpoint analyses. The results showed improvements across the reported response measures. The pCR rate was 33% with visugromab plus nivolumab compared with 8% with nivolumab plus placebo. MPR was 60% versus 23%, and ORR was 60% versus 15%. The combination arm included seven complete responses among 15 evaluable patients in the radiographic assessment. Independent blinded central assessment was largely concordant with local evaluations. These findings suggest that targeting GDF-15 may enhance the activity of PD-1 inhibition in this neoadjuvant setting. However, the study was not designed to establish definitive long-term survival benefit, and the response rates require confirmation in larger clinical trials.
Response Findings May Expand Bladder-Sparing Treatment Options
The GDFATHER-NEO findings also highlighted the potential relevance of deeper tumor responses to bladder preservation. A greater proportion of patients in the visugromab-plus-nivolumab group underwent bladder-sparing re-TURBT compared with the nivolumab-plus-placebo group, at 37.5% versus 20.0%. Among patients who achieved pCR in the combination arm, four of five retained their bladder after re-TURBT alone. At a median follow-up of 15.7 months, no recurrences were observed among patients who achieved pCR in either treatment group; this included five patients in the combination arm and one in the control arm. Median event-free survival (EFS) had not been reached in either group, with follow-up limited to approximately one year after surgery. These observations are encouraging but remain preliminary because of the small number of patients and limited duration of follow-up. Bladder-sparing treatment may be an important consideration for eligible patients, but decisions about avoiding or delaying radical cystectomy require careful clinical assessment and longer-term evidence. The safety findings were consistent with previously reported data, and the combination was generally well tolerated. Treatment-related adverse events were predominantly mild to moderate and consistent with the known safety profiles of checkpoint inhibitors. No treatment-related discontinuations or treatment-related delays to surgery were reported in the visugromab arm. The study also found that baseline infiltration by proliferating CD8-positive T cells correlated with response to the combination. This exploratory observation may help inform future research into biomarkers associated with treatment response, but it does not yet establish a validated method for selecting patients. Together, the efficacy and safety findings provide a basis for further investigation of GDF-15 neutralization in earlier treatment settings for selected solid tumors.
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CatalYm Advances Visugromab Across Multiple Cancer Settings
CatalYm is continuing clinical development of visugromab through randomized Phase 2b studies in other high-need indications, including first- and second-line non-small cell lung cancer (NSCLC), second-line hepatocellular carcinoma and cancer-associated cachexia. These programs are intended to investigate whether GDF-15 neutralization can improve outcomes in different disease settings, including cancers treated with immune checkpoint inhibitors. CatalYm Chief Medical Officer Sujata Rao, M.D., said the final GDFATHER-NEO results, supported by independent central assessment and more than one year of follow-up, strengthen the clinical evidence for visugromab and support its evaluation in additional solid tumors. Study investigator Andrea Necchi, M.D., of IRCCS San Raffaele Hospital, highlighted the need for better neoadjuvant treatment options and the potential significance of the response and bladder-sparing findings. The company is also investigating visugromab’s potential to mitigate cancer-associated cachexia, a condition involving weight loss and reduced appetite that can affect patients with advanced cancer. According to CatalYm, GDF-15 contributes to cachexia through signaling involving the GFRAL pathway in the brainstem, providing an additional rationale for studying the antibody beyond its potential effects on tumor immunity. Founded in 2016 and based in Munich, Germany, and San Francisco, USA, CatalYm is developing visugromab as an anti-GDF-15 therapy for solid tumors and cachexia. The GDFATHER-NEO results add clinical evidence supporting the company’s development strategy, but visugromab remains investigational. Additional trials will be needed to establish the durability of response, the impact on survival and the potential role of the treatment in routine care.
Source: CatalYm ,Press release
