CatalYm Initiates Phase 2b Trial of Visugromab in Second-Line Hepatocellular Carcinoma Treatment
Key Insights
CatalYm has dosed the first patient in the GDFATHER-HCC-01 trial, evaluating visugromab combined with nivolumab and lenvatinib for patients with unresectable or metastatic hepatocellular carcinoma (search) who progressed after first-line anti-PD-(L)1 (search) therapy.
The anti-GDF-15 (search) antibody visugromab demonstrated encouraging anti-tumor activity in earlier trials, with a median duration of response of 21.4 months in advanced-stage, anti-PD-(L)1 (search) relapsed/refractory HCC patients.
The global Phase 2b study will enroll approximately 104 participants across 40 sites, with progression-free survival as the primary endpoint and potential cachexia mitigation as an exploratory objective.
CatalYm has announced the dosing of the first patient in its GDFATHER-HCC-01 trial, a Phase 2b study evaluating visugromab in combination with chemoimmunotherapy as second-line treatment for patients with unresectable or metastatic hepatocellular carcinoma (search) (HCC). The trial targets patients who have progressed following first-line treatment with an anti-PD-(L)1 (search)-based therapy.
Trial Design and Treatment Strategy
The study will assess a treatment strategy combining visugromab with the PD-1 (search) inhibitor nivolumab and the multi-target tyrosine kinase inhibitor lenvatinib. The trial consists of two parts: an open-label safety run-in to confirm the recommended dose for expansion, followed by a randomized, double-blind phase evaluating visugromab plus nivolumab plus lenvatinib versus double placebo plus lenvatinib.
The global, randomized, blinded Phase 2b study will enroll approximately 104 participants across 40 sites in North America, Europe and Asia-Pacific. The primary endpoint is progression-free survival (PFS) assessed by local investigators, with key secondary endpoints including overall survival (OS), independently assessed PFS, and objective response rate (ORR).
Mechanism of Action and Previous Results
Visugromab is a monoclonal antibody that neutralizes Growth Differentiation Factor-15 (GDF-15 (search)), an immunosuppressive cytokine exploited by tumor cells to promote immune evasion and resistance to anti-PD-(L)1 (search) therapies. By neutralizing GDF-15, visugromab aims to restore anti-tumor immune responses to improve outcomes in a setting where 5-year overall survival remains as low as 18%.
In the exploratory Phase 1/2a GDFATHER trial, visugromab demonstrated encouraging anti-tumor activity when combined with an anti-PD-1 (search) antibody in advanced-stage, anti-PD-(L)1 (search) relapsed/refractory HCC patients, demonstrating deep and durable responses, with a median duration of response of 21.4 months and a favorable safety profile.
Clinical Context and Unmet Need
Hepatocellular carcinoma (search) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. The five-year survival rate for HCC is only 18%, second lowest among common cancers. While checkpoint inhibitors have become a first-line standard of care, most patients with advanced-stage HCC ultimately experience disease progression or relapse. Treatment options in the second-line setting remain limited, underscoring the urgent need for more effective and well-tolerated therapies.
"HCC is the third leading cause of cancer-related deaths globally and continues to present immense clinical challenges, especially in patients who progress on immunotherapy," said Sujata Rao, MD, Chief Medical Officer at CatalYm. "This new trial is designed to combine the immune-restoring properties of visugromab with a checkpoint inhibitor and the standard of care tyrosine kinase inhibitor. With this approach we aim to improve clinical outcomes for HCC patients with limited treatment options."
Addressing Cancer Cachexia
The study will also explore visugromab's potential to mitigate cancer cachexia (search) using the Functional Assessment of the Anorexia and Cachexia Therapy questionnaire (FAACT-ACS), as muscle wasting and weight loss are common in HCC and known to negatively affect treatment tolerance and clinical outcomes. Cancer cachexia affects nearly one in four patients with HCC at diagnosis.
"Expanding into HCC represents a pivotal step in our strategy to bring visugromab to additional high-need tumor types," said Scott Clarke, Chief Executive Officer at CatalYm. "Visugromab's dual potential to restore immune sensitivity and address cancer cachexia (search), which affects nearly one in four patients with HCC at diagnosis, underpins our approach in this study. By combining our antibody with proven standards of care, we aim to shift the treatment paradigm and ultimately improve survival and quality of life for patients who have few options today."
Development Pipeline Expansion
The GDFATHER-HCC-01 trial represents the initiation of the third Phase 2b study of visugromab, expanding development into hepatocellular carcinoma (search) following first and second-line NSCLC programs. CatalYm is advancing visugromab into multiple Phase 2b studies including first-line metastatic non-squamous NSCLC (search) and second-line metastatic non-squamous NSCLC.