Key Discoveries from the AMADEUS Clinical Trial on Cancer Treatment

The Cancer Research Institute (CRI) is excited to share the findings from the AMADEUS clinical trial, which were recently published in the in Journal of Experimental Medicine. This study, led by  Padmanee Sharma, MD, PhD, Professor in the departments of Genitourinary Medical Oncology and Immunology, Scientific Director for the Immunotherapy Platform at the University of Texas MD Anderson Cancer Center, Co-Director of the Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center, and CRI Scientific Advisory Council Member, sheds light on how biomarkers can predict how patients respond to immune checkpoint inhibitor (ICI) treatments like nivolumab and ipilimumab.

CRI Scientific Advisory Council Member F. Stephen Hodi, from the Dana-Farber Cancer Institute, CRI’s former CEO and former Director of Scientific Affairs Jill O’Donnell-Tormey, PhD, and former Director of the CRI-Anna Maria Kellen Clinical Accelerator Venture Fund Vanessa M. Hubbard-Lucey, PhD, MBA, and Danny N. Khalil from Memorial Sloan Kettering Cancer Center were also part of the study.

ICIs have revolutionized cancer treatment by helping the immune system better recognize and attack cancer cells. However, not all patients respond equally to these treatments, which led researchers to investigate these discrepancies.

A key focus of the study was on CD8 T cells, a type of immune cell that plays a crucial role in fighting cancer. Tumors with higher levels of CD8 T cells often respond better to ICI treatments. In the trial, a combination of nivolumab and ipilimumab was effective for patients with low levels of CD8 T cells in their tumors. The treatment increased these cells’ tumor infiltration, improving overall treatment response.

The study also found that patients who responded well to treatment often had specific genetic signatures related to inflammation in their tumors before they started therapy. These signatures became more pronounced during treatment, indicating a strong immune response.

Not all tumors with increased CD8 T cell levels responded to treatment, suggesting other factors, like the presence of certain immune cells and genetic markers, also play a role in determining the therapy’s effectiveness. Researchers are now exploring additional biomarkers to better predict which patients will benefit most from ICI treatments.

The results from the AMADEUS trial provide a strong foundation for future research aimed at developing personalized cancer treatments based on individual genetic and immune profiles. By better understanding how different tumors interact with the immune system, scientists are creating a world immune to cancer.