Epacadostat

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Epacadostat is an investigational drug that acts as an inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). It is being studied for its potential use in cancer immunotherapy.

Mechanism of Action

Epacadostat works by inhibiting the activity of IDO1, an enzyme that is involved in the metabolism of tryptophan into kynurenine. IDO1 is often overexpressed in various types of tumors, leading to an immunosuppressive environment that allows cancer cells to evade the immune system. By blocking IDO1, epacadostat aims to restore the immune system's ability to recognize and attack cancer cells.

Clinical Development

Epacadostat has been evaluated in several clinical trials for its efficacy and safety in treating different types of cancer. It has been studied both as a monotherapy and in combination with other immunotherapeutic agents, such as checkpoint inhibitors like pembrolizumab and nivolumab.

Key Clinical Trials

• ECHO-301/KEYNOTE-252: This was a Phase 3 clinical trial that evaluated the combination of epacadostat and pembrolizumab in patients with advanced melanoma. The trial did not meet its primary endpoint of progression-free survival.
• ECHO-202/KEYNOTE-037: This Phase 1/2 trial investigated the combination of epacadostat and pembrolizumab in patients with various advanced solid tumors, including non-small cell lung cancer, renal cell carcinoma, and urothelial carcinoma.

Side Effects

The most common side effects observed in clinical trials of epacadostat include fatigue, nausea, rash, and diarrhea. Serious adverse events have also been reported, including immune-related adverse events.

Future Directions

Despite the setback in the ECHO-301/KEYNOTE-252 trial, research continues to explore the potential of IDO1 inhibitors like epacadostat in combination with other therapeutic agents. Ongoing studies are investigating different dosing regimens, combinations with other immunotherapies, and the identification of biomarkers that may predict response to treatment.

See Also

• Indoleamine 2,3-dioxygenase
• Immunotherapy
• Checkpoint inhibitor
• Cancer