CatalYm doses first patient in Phase 2b GDFATHER-HCC-01 trial evaluating anti-GDF-15 antibody visugromab with nivolumab and lenvatinib as second-line treatment for advanced hepatocellular carcinoma.
Written By: Mahathi Palivela PharmD
Reviewed By: Pharmacally Editorial Team
Phase 2b Trial Initiated in Post-Immunotherapy HCC
CatalYm announced that the first patient has been dosed in the Phase 2b GDFATHER-HCC-01 trial (NCT07219459), evaluating the anti-GDF-15 antibody visugromab in combination with nivolumab and lenvatinib for patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progressed after first-line anti-PD-(L)1–based therapy. The study investigates the triple regimen as a second-line treatment option in a population with limited therapeutic alternatives.
Two-Part Global Study Design
The global trial is designed in two parts. An initial open-label safety run-in will evaluate visugromab with nivolumab and lenvatinib to determine the recommended dose for expansion. This will be followed by a randomized, double-blind portion comparing visugromab plus nivolumab plus lenvatinib against double placebo plus lenvatinib. The study aims to enroll approximately 104 participants across around 40 sites in North America, Europe, and the Asia-Pacific region.
Endpoints Include Survival and Cachexia Outcomes
The primary endpoint is progression-free survival assessed by local investigators. Key secondary endpoints include overall survival, independently assessed progression-free survival, and objective response rate. The trial will also explore visugromab’s potential effect on cancer cachexia using the Functional Assessment of the Anorexia and Cachexia Therapy questionnaire, given that weight loss and muscle wasting are common in HCC and can affect treatment tolerance and outcomes.
Visugromab Targets GDF-15–Mediated Immune Suppression
Visugromab is a monoclonal antibody targeting Growth Differentiation Factor-15 (GDF-15), an immunosuppressive cytokine associated with tumor immune evasion and resistance to checkpoint inhibitors. By neutralizing GDF-15, the therapy is intended to restore anti-tumor immune responses. In the exploratory Phase 1/2a GDFATHER study (NCT04725474), visugromab combined with an anti-PD-1 antibody demonstrated durable anti-tumor activity in advanced, anti-PD-(L)1 relapsed or refractory HCC, with a median duration of response of 21.4 months and a favorable safety profile.
Company Leadership Highlights Clinical Rationale
CatalYm’s Chief Medical Officer, Sujata Rao, stated that HCC remains a major clinical challenge, particularly after progression on immunotherapy, and noted that the trial is designed to combine immune restoration with checkpoint inhibition and tyrosine kinase inhibition to improve outcomes.
Chief Executive Officer Scott Clarke added that expanding visugromab into HCC aligns with the company’s strategy to target high-need tumor types, highlighting the therapy’s potential to restore immune sensitivity and address cancer cachexia in this patient population.
High Unmet Need in Hepatocellular Carcinoma
Hepatocellular carcinoma is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. Despite checkpoint inhibitors becoming a first-line standard, most patients with advanced disease eventually relapse or progress, and second-line treatment options remain limited.
Reference
CatalYm Doses First Patient in Phase 2b Trial Evaluating Visugromab in Combination with Chemoimmunotherapy as Second-Line Treatment in Unresectable/Metastatic Hepatocellular Carcinoma, 07 April 2026, CatalYm Doses First Patient in Phase 2b Trial Evaluating Visugromab in Combination with Chemoimmunotherapy as Second-Line Treatment in Unresectable/Metastatic Hepatocellular Carcinoma – Catalym
First-in-Human Study of the GDF-15 Neutralizing Antibody Visugromab (CTL-002) in Patients with Advanced Cancer (GDFATHER) (GDFATHER), ClinicalTrials.gov ID NCT04725474, https://clinicaltrials.gov/study/NCT04725474
About the Writer
Mahathi Palivela is pursuing PharmD and has a strong interest in Clinical Pharmacy and Patient safety. She is passionate about handling and analyzing patient data, and translating clinical insights into clear, meaningful summaries. She aims to apply this interest in Medical Writing and Pharmacovigilance, focusing on improving patient outcomes through careful data interpretation and communication.