The AMADEUS Trial

Why This Trial

Checkpoint inhibitors offer cancer patients a chance at long-term survival by taking the brakes off the immune system so it can attack tumors. But do two drugs work better than one?

It’s an important question that patients face. One checkpoint inhibitor may work for some, but not all. A combination may work better, but often comes with more side effects and a higher cost.

That’s where biomarkers come in. The right biomarkers could help determine what works best for which patients, so they get treatment that’s right for them.

Part of the puzzle is figuring out when cancer is most vulnerable to immunotherapy. To do that, you have to take the temperature of the tumor. Is the tumor hot or cold? We’re also searching for biomarkers to help us answer that question.

Hot v. Cold Tumors

The theory is that a “cold” tumor will not respond to immunotherapy, including checkpoint inhibition, because too few T-cells are present to effectively kill the cancer. A “hot” tumor has more cancer-fighting T-cells and should respond to treatment.

But what if we’re using the wrong thermometer? What if we aren’t measuring all the right things that could tell us how warm a tumor is, if it’s able to respond to immunotherapy?

This trial is designed to find the answers. In addition to the amount of T-cells in a tumor, we are examining multiple factors – other potential biomarkers – that could indicate if a tumor is hot or cold and will respond to one or more checkpoint inhibitors.

About the Study

In this prospective study, patients will first undergo a tumor biopsy. Patients with a higher concentration of T-cells (or a hot tumor) will receive a single checkpoint inhibitor, nivolumab. Patients with a lower concentration of T-cells (a cold tumor) will undergo a combination of nivolumab plus ipilimumab.

Through a battery of tests – including gene sequencing, protein analysis, imaging and gut microbiome analysis – we will evaluate how the immune system is changing before, during and after treatment.

This uniquely comprehensive collection of biomarker data will allow us to create a “heat map” of cancer that doctors can use to guide patient treatment in the future.

Who’s Eligible

• Metastatic cancer patients (up to 80)
• Multiple types of solid tumors

Treatments Tested

• Nivolumab
• Nivolumab plus ipilimumab

Where We’re At Now

The study began enrolling patients in September 2018.

Findings presented at the 2021 ASCO Annual Meeting showed the combination of ipilimumab and nivolumab has the ability to drive CD8 T cells into a wide variety of tumors with low levels of CD8 T cells at baseline – turning them “hot” – and can lead to clinical responses.