2023 World Conference on Lung Cancer (Posters)-EP11.02. Phase I Study of Epacadostat in Combination with Sirolimus in Solid Tumors and PK Data.

EP11.02. Phase I Study of Epacadostat in Combination with Sirolimus in Solid Tumors and PK Data. - PDF(Slides)

Pdf Summary

This study investigated the use of the inhibitor Epacadostat (E) in combination with the mTOR inhibitor Sirolimus (S) to address potential resistance mechanisms. E inhibits IDO1, leading to decreased immunosuppression and increased T cell proliferation. However, inhibition of IDO1 can also lead to suppression of autophagy and inadequate cancer antigen exposure. <br /><br />The study conducted a Phase I trial with dose escalation, enrolling patients with solid tumors refractory to standard therapy. The starting doses were 300mg of E twice daily and 1mg of S once daily. Adverse events attributed to the study agents included anemia, vertigo, constipation, diarrhea, nausea, stomach pain, elevated liver enzymes, decreased white blood cell count, anorexia, hypokalemia, dizziness, serotonin syndrome, dyspnea, and skin rash.<br /><br />The dose escalation treatment schedule included different combinations of E and S, with doses ranging from 100mg of E and 3mg of S to 400mg of E and 6mg of S. The pharmacokinetic (PK) data showed consistent levels of E and sirolimus in the plasma.<br /><br />The study concluded that the combination of E and S showed results consistent with previous reports, with E accumulating in a dose-proportional manner. The dose level of 400mg of E twice daily was able to inhibit over 80% of kynurenine production. This combination could potentially be used with other immunotherapy agents to promote T cell activation and suppression of T regulatory cells, particularly in the treatment of advanced non-small cell lung cancer resistant to checkpoint inhibitors.

Asset Subtitle

chao Huang

Meta Tag

Speaker chao Huang

Topic Metastatic NSCLC: Immunotherapy - Prospective

Keywords

Epacadostat

mTOR inhibitor

resistance mechanisms

IDO1 inhibition

immunosuppression

T cell proliferation

autophagy suppression

Phase I trial

solid tumors

checkpoint inhibitors