Visugromab is a new type of medicine, a monoclonal antibody, currently being investigated for treating various cancers. It works by targeting a specific protein in the body that can interfere with the immune system’s ability to fight cancer. This novel approach aims to improve treatment outcomes for patients with certain types of advanced cancers.
Understanding GDF-15 and Immune Evasion
Growth Differentiation Factor-15 (GDF-15) is a protein that is typically present at low levels in healthy tissues. However, in many cancers, tumor cells produce high amounts of GDF-15, which can then act as a signal to suppress the body’s immune response. This elevated GDF-15 creates an environment where immune cells find it harder to get into tumors and launch an effective attack.
GDF-15 can promote the generation of certain immune cells, like regulatory T cells, which further dampen anti-tumor immunity. It also interferes with the ability of T cells to stick to and enter tumor tissues by blocking a specific pathway known as the LFA-1/ICAM-1 axis. Elevated GDF-15 levels in cancer patients have been linked to a poorer outlook and reduced survival.
This protein’s presence can also contribute to resistance to existing immunotherapies, such as anti-PD-1/PD-L1 treatments. Tumors can increase GDF-15 production as a way to adapt and survive when faced with therapeutic pressure from various cancer treatments.
How Visugromab Works
Visugromab functions as a monoclonal antibody, a type of engineered protein designed to target specific molecules in the body. In this case, visugromab specifically binds to and neutralizes Growth Differentiation Factor-15 (GDF-15). By blocking GDF-15, visugromab aims to remove the “brake” that tumors place on the immune system.
This neutralization of GDF-15 helps to “unblock” the immune system, allowing immune cells, such as T-cells, to become more active. It promotes the infiltration of these immune cells into the tumor microenvironment, which is the area immediately surrounding the cancer cells.
The action of visugromab also supports the priming of T cells by dendritic cells and enhances the tumor-killing effects of both T cells and natural killer (NK) cells. This comprehensive immune reactivation enables the body’s natural defenses to recognize and attack cancer cells more efficiently.
Clinical Development and Potential Uses
Visugromab is currently undergoing investigation in Phase 2 clinical studies. The drug is being explored for use in several types of solid tumors, including non-small cell lung cancer (NSCLC), urothelial cancer (UC), hepatocellular cancer (HCC), and muscle-invasive bladder cancer (MIBC).
A common strategy in these trials is to use visugromab in combination with other immunotherapies, particularly anti-PD-1 inhibitors like nivolumab. This combination approach is based on the idea that these treatments can work together synergistically. While anti-PD-1 therapies help to release immune cells from a different type of “brake,” visugromab tackles the GDF-15-mediated suppression, potentially allowing for a more robust and complete immune response against the cancer.
The ongoing Phase 2a “GDFATHER” trial (NCT04725474) is investigating visugromab in combination with a PD-1 checkpoint inhibitor in various advanced-stage solid tumors. This study includes patients who have not responded to or have relapsed after previous anti-PD-1/PD-L1 treatments. An additional exploratory Phase 2 study, GDFATHER-NEO (NCT06059547), is evaluating visugromab alongside neoadjuvant nivolumab in treatment-naive muscle-invasive bladder cancer patients, exploring its potential in earlier stages of disease.
Clinical Trial Findings and Patient Experience
Clinical trials have shown promising results for visugromab, particularly in combination with anti-PD-1 treatments. The drug has demonstrated durable anti-tumor efficacy. For example, in patients with non-small cell lung cancer and urothelial cancer, responses have lasted for over 16 and 15 months, respectively.
In studies, the combination of visugromab with nivolumab has shown a safety profile comparable to nivolumab treatment alone, with a low incidence of severe side effects. Only a small percentage, approximately 3.7%, of patients experienced severe treatment-related adverse events in one Phase 2a trial.
Visugromab has shown particular promise in patients with advanced cancers that have relapsed or are refractory to prior anti-PD-1/PD-L1 therapies. In these heavily pretreated patients, visugromab has induced confirmed partial and complete responses. A notable finding is that many responders experienced deeper tumor shrinkage than they had with their previous anti-PD-1/PD-L1 treatments, with some achieving complete remissions they had not reached before.
Beyond its direct anti-tumor effects, visugromab may also alleviate certain treatment-related side effects. Elevated GDF-15 levels are known to contribute to cancer-associated cachexia, a syndrome characterized by severe weight loss, muscle wasting, and loss of appetite. By neutralizing GDF-15, visugromab has the potential to mitigate these effects, potentially improving patients’ quality of life and their ability to tolerate ongoing cancer treatments.