CatalYm Initiates Phase 2/3 Trial of Visugromab in Cancer Cachexia with First Patient Dosed
CatalYm has announced an important milestone in its clinical development pipeline with the dosing of the first patient in its pivotal Phase 2/3 VINCIT trial (Visugromab IN Cachexia International Trial). This global study is designed to evaluate the safety and efficacy of visugromab, the company’s lead investigational therapy, in patients suffering from cancer-associated cachexia—a serious and often overlooked complication of advanced malignancies.
The VINCIT trial represents a significant advancement in the effort to address cachexia, a complex metabolic syndrome that remains one of the most challenging conditions in oncology care. The study is structured as a randomized, double-blind, placebo-controlled Phase 2/3 trial and is expected to enroll approximately 518 patients worldwide. Participants will include individuals diagnosed with cachexia linked to a range of advanced cancers, including Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), and other solid tumors.
Cancer cachexia is characterized by a combination of involuntary weight loss, progressive muscle wasting, and a decline in physical function. Unlike simple malnutrition, cachexia cannot be reversed by conventional nutritional support alone and is often accompanied by systemic inflammation and metabolic abnormalities. The condition significantly diminishes patients’ quality of life, reduces tolerance to anticancer therapies, and is associated with poorer clinical outcomes. In certain cancers, cachexia can affect up to 70% of patients and is estimated to contribute to 20–40% of cancer-related deaths, highlighting the urgent need for effective therapeutic interventions.
Despite its clinical significance, there are currently no approved pharmacological treatments specifically targeting cancer cachexia. This gap in care underscores the importance of innovative approaches such as visugromab, which is designed to address the underlying biological mechanisms driving the condition. A key factor implicated in cachexia is Growth Differentiation Factor-15 (GDF-15), a stress-induced cytokine produced by tumors and other tissues. Elevated levels of GDF-15 have been linked to appetite suppression, weight loss, and metabolic dysfunction, making it a compelling therapeutic target.
Visugromab is a humanized monoclonal antibody that selectively targets GDF-15, aiming to neutralize its effects and restore metabolic balance. By inhibiting GDF-15 signaling, visugromab has the potential not only to mitigate the symptoms of cachexia but also to improve patients’ overall response to cancer treatments. This dual mechanism—addressing both metabolic decline and immune suppression—positions visugromab as a promising candidate in the evolving landscape of oncology therapeutics.
According to Sujata Rao, MD, Chief Medical Officer at CatalYm, cachexia remains one of the most debilitating and under-addressed complications in cancer care. She emphasized that the initiation of the VINCIT trial builds on encouraging findings from earlier studies, particularly with respect to weight gain observed in treated patients. These results, combined with growing scientific evidence supporting the role of GDF-15 in metabolic wasting, reinforce the rationale for advancing visugromab into later-stage clinical development.
Scott Clarke, Chief Executive Officer of CatalYm, further highlighted the broader implications of targeting GDF-15. He noted that this cytokine is not merely a byproduct of cancer progression but plays a central role in both immune resistance and metabolic deterioration. By intervening in this pathway, visugromab could potentially open a new therapeutic avenue for patients whose outcomes are severely compromised by cachexia. This perspective reflects a growing recognition within the scientific community that addressing systemic effects of cancer is as important as targeting the tumor itself.
The VINCIT trial is designed with an adaptive structure to optimize dose selection and maximize the likelihood of clinical success. In the first part of the study, patients will be randomized to receive one of three different dose levels of visugromab or a placebo, administered every four weeks over a 12-week period. Interim analyses will be conducted to identify the most effective and well-tolerated dose. This selected dose will then be carried forward into the second phase of the trial.
In Part 2, participants will be randomized in a 2:1 ratio to receive either visugromab or placebo for an extended duration of up to 52 weeks. This phase aims to provide more comprehensive data on long-term efficacy and safety. The global nature of the trial, with clinical sites spanning multiple regions, ensures a diverse patient population and enhances the generalizability of the findings.
The primary endpoints of the VINCIT trial focus on changes in body weight and appetite over the initial 12-week treatment period. These measures are critical indicators of cachexia progression and patient well-being. Secondary endpoints will assess a broader range of outcomes, including muscle mass, physical function, levels of physical activity, tumor response, overall survival, and patient-reported quality of life. Safety and tolerability will also be closely monitored throughout the study. Additionally, exploratory analyses will examine pharmacodynamic markers and potential biomarkers to better understand the biological effects of visugromab.
The advancement of visugromab into a Phase 2/3 trial is supported by data from the earlier GDFATHER study, an exploratory Phase 1/2a trial that evaluated the therapy in combination with Nivolumab. In that study, visugromab demonstrated encouraging anti-tumor activity and a favorable safety profile in patients with relapsed or refractory cancers, including NSCLC, hepatocellular carcinoma, and urothelial cancer. Notably, the trial also provided early clinical evidence of visugromab’s potential to alleviate cachexia, with some patients experiencing meaningful weight gain—particularly those who had significant weight loss at the start of treatment.
These findings suggest that targeting GDF-15 may have a dual therapeutic benefit: enhancing immune response against tumors while simultaneously counteracting the metabolic decline associated with cachexia. This integrated approach could represent a paradigm shift in oncology, where treatments are designed not only to control tumor growth but also to improve patients’ overall health and resilience.
As the VINCIT trial progresses, it is expected to generate critical data that could pave the way for the first approved therapy specifically for cancer cachexia. If successful, visugromab could address a major unmet need in oncology, offering hope to patients who currently have limited options for managing this debilitating condition.
In summary, the initiation of the VINCIT trial marks a pivotal moment for CatalYm and the broader oncology community. By targeting a key driver of metabolic dysfunction and immune suppression, visugromab holds the potential to transform the treatment landscape for cancer-associated cachexia and improve outcomes for patients facing advanced disease.
About cancer cachexia and GDF-15
Cancer cachexia is a complex and debilitating syndrome that affects up to 70% of patients with advanced cancer1. The condition is closely linked to elevated GDF-15 levels, which drive severe and progressive weight loss, muscle wasting, reduced appetite, and metabolic disturbances through activation of the GFRAL receptor in the brainstem. Unlike starvation, cachexia cannot be fully reversed with nutritional support alone, as it is driven by a combination of systemic inflammation, tumor-derived factors, and metabolic dysregulation. This condition significantly diminishes the quality of life for cancer patients and severely impacts their ability to tolerate and respond to treatment, often leading to poorer outcomes and increased mortality.
About Visugromab
Visugromab is a monoclonal antibody that neutralizes Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant produced by tumors which fosters immunotherapy resistance and drives cachexia in people with cancer. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation and induction of interferon-γ. In addition, visugromab also mitigates cancer cachexia, a severe condition affecting a significant number of advanced cancer patients by inhibiting the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients.
About CatalYm
CatalYm is developing visugromab, a first-in-class anti-GDF-15 antibody, in solid tumors and cachexia. In its first-in-human Phase 1/2a study, visugromab demonstrated deep and durable anti-tumor efficacy with long-lasting objective responses in relapsed and checkpoint refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. In addition, data from the same study demonstrated that visugromab can significantly counteract the effects of cachexia in these patients.
This data was published in Nature and presented at the International Conference on Sarcopenia, Cachexia & Wasting Disorders. CatalYm is now advancing visugromab into multiple Phase 2b studies including first-line metastatic non-squamous NSCLC (NCT07098988), second-line metastatic non-squamous NSCLC (NCT07246863), second-line hepatocellular carcinoma (NCT07219459) and cachexia (NCT07112196).
Founded in 2016 and based in Munich, Germany and San Francisco, USA, CatalYm is backed by leading international investors including Canaan Partners, Omega Funds, Bioqube Ventures, Forbion, Jeito Capital, Brandon Capital, Gilde Healthcare, Novartis Venture Fund, Vesalius, Bayern Kapital, BioGeneration Ventures, and Coparion.
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