CatalYm has announced the dosing of the first patient in its randomized Phase 2b GDFATHER-NSCLC-01 trial, marking a significant milestone in the development of visugromab, a first-in-class anti-GDF-15 antibody for cancer treatment. The trial evaluates visugromab in combination with standard-of-care chemoimmunotherapy compared to placebo plus chemoimmunotherapy as first-line treatment for patients with newly diagnosed metastatic non-squamous non-small cell lung cancer.
Novel Mechanism Targets Immunotherapy Resistance
Visugromab is a humanized monoclonal antibody designed to neutralize Growth Differentiation Factor-15 (GDF-15), a tumor-derived cytokine that plays a central role in immune suppression and anti-PD-(L)-1 resistance. According to CatalYm, 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.
The therapeutic approach addresses a critical unmet need in NSCLC treatment, where 70-85% of patients either exhibit primary resistance to PD-1 blockade or develop acquired resistance to immunotherapy. "GDF-15 plays a critical role in shielding tumors from immune attack, limiting the effectiveness of current immunotherapies," said Dr. Sujata Rao, Chief Medical Officer at CatalYm.
Promising Early Clinical Results
CatalYm demonstrated visugromab's therapeutic potential in the exploratory Phase 1/2a GDFATHER trial, where the combination of visugromab and an anti-PD-1 inhibitor led to deep and durable responses across multiple solid tumor types while maintaining a favorable safety profile. The treatment also showed potential to mitigate cancer cachexia, enhancing patients' quality of life and treatment tolerability.
"Our clinical trials have clearly shown visugromab's impact for solid tumor patients in multiple settings," said Scott Clarke, Chief Executive Officer at CatalYm. "Given the strong anti-tumor effect with long durability, we believe that visugromab is uniquely positioned to demonstrate compelling efficacy as part of a first-line treatment regimen."
Phase 2b Trial Design and Endpoints
The randomized, blinded, placebo-controlled Phase 2b GDFATHER-NSCLC-01 trial will enroll approximately 107 patients across multiple sites in the US, EU and Switzerland. The trial consists of an initial non-randomized safety run-in, followed by a randomized part. The primary endpoint is objective response rate (ORR), with key secondary endpoints including duration of response (DOR), complete and partial response rates (CR and PR), progression-free survival (PFS), overall survival (OS), body weight trends as well as safety and tolerability parameters.
Addressing Critical Medical Need
Lung cancers remain the leading cause of cancer-related mortality globally, with non-small cell lung cancers accounting for approximately 87% of the 210,000 annual lung cancer diagnoses in the US. Five-year survival rates in the US for non-squamous NSCLC are particularly low: 12.8% for adenocarcinoma and 5.1% for large-cell carcinoma.
Additional Clinical Development
Beyond the NSCLC trial, CatalYm is advancing visugromab across multiple indications. Results from a blinded, exploratory Phase 2 trial of nivolumab and visugromab or placebo as neoadjuvant treatment in patients with muscle-invasive bladder cancer will be announced at ESMO 2025 in a late-breaking oral presentation.
The company will also present long-term follow-up data from the GDFATHER-01 Phase 1/2 trial demonstrating deep and durable remissions in heavily pretreated, anti-PD1/-L1 relapsed/refractory patients across multiple tumor types including non-squamous NSCLC, urothelial cancer, and hepatocellular cancer.
Visugromab's dual mechanism of action extends beyond tumor response, as the antibody also mitigates cancer cachexia by inhibiting the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients. CatalYm is advancing visugromab into multiple Phase 2b studies including cachexia treatment.
