CatalYm’s lead drug candidate, visugromab, a monoclonal antibody targeting the immunosuppressant GDF-15, has shown promising results in a Phase 1/2a trial for various solid tumors. The study, published in •Nature•, revealed visugromab’s ability to induce significant and durable cancer remission, especially when combined with the PD-1 inhibitor nivolumab, in patients with late-stage cancers resistant to anti-PD-(L)1 therapies. The research highlights the potential of GDF-15 inhibition as a novel approach to overcome immunotherapy resistance.
This development holds considerable promise for cancer treatment. Current immunotherapies, while effective for some, often face limitations due to developed resistance mechanisms employed by tumor cells. Visugromab’s ability to counteract GDF-15, a key player in this resistance, offers a potential solution to enhance and broaden the efficacy of existing immunotherapies like nivolumab. The observed deep and durable responses, including complete remissions, in patients with limited treatment options underscore the potential clinical impact of this approach. Furthermore, the alleviation of cachexia, a debilitating syndrome linked to elevated GDF-15, offers a potential improvement in quality of life for patients.
The Nature publication presents comprehensive data from the GDFATHER Phase 1/2a trial. Results demonstrate that visugromab, in combination with nivolumab, achieved robust responses in patients with relapsed or refractory non-small cell lung cancer, urothelial cancer, and hepatocellular cancer. More than half of the responding patients experienced deeper remissions compared to their initial checkpoint inhibitor treatment. The study also provides substantial translational research demonstrating visugromab’s mechanism of action: it promotes T-cell influx and proliferation within the tumor microenvironment and induces an Interferon-γ signature, both alone and in combination with nivolumab. Further immunogenomic analyses confirm the broad influence of GDF-15 on the tumor microenvironment and its immune landscape.
Visugromab’s success in early clinical trials positions it as a potential game-changer in cancer immunotherapy. The ability to overcome resistance to established checkpoint inhibitors, combined with a promising safety profile and durable responses, opens avenues for new treatment strategies across multiple cancer types. The initiation of a broad Phase 2b program in earlier treatment settings suggests a rapid advancement of visugromab toward broader clinical application and holds potential for significantly improved patient outcomes in the near future.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
