Phase I/II Sequencing Study of Azacitidine, Epacadostat, and Pembrolizumab in Advanced Solid Tumors

Authors

Jason J Luke
Marwan Fakih
Charles Schneider
E Gabriela Chiorean
Johanna Bendell
Rebecca Kristeleit
Razelle Kurzrock
Sarah P Blagden
Irene Brana
Laura W Goff
Kevin O'Hayer
Ryan Geschwindt
Michael Smith
Feng Zhou
Aung Naing

Publication Date

6-1-2023

Journal

British Journal of Cancer

DOI

10.1038/s41416-023-02267-1

PMID

37087488

PMCID

PMC10241827

PubMedCentral® Posted Date

4-22-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-inducible enzyme, contributes to tumor immune intolerance. Immune checkpoint inhibition may increase interferon levels; combining IDO1 inhibition with immune checkpoint blockade represents an attractive strategy. Epigenetic agents trigger interferon responses and may serve as an immunotherapy priming method. We evaluated whether epigenetic therapy plus IDO1 inhibition and immune checkpoint blockade confers clinical benefit to patients with advanced solid tumors.

Methods: ECHO-206 was a Phase I/II study where treatment-experienced patients with advanced solid tumors (N = 70) received azacitidine plus an immunotherapy doublet (epacadostat [IDO1 inhibitor] and pembrolizumab). Sequencing of treatment was also assessed. Primary endpoints were safety/tolerability (Phase I), maximum tolerated dose (MTD) or pharmacologically active dose (PAD; Phase I), and investigator-assessed objective response rate (ORR; Phase II).

Results: In Phase I, no dose-limiting toxicities were reported, the MTD was not reached; a PAD was not determined. ORR was 5.7%, with four partial responses. The most common treatment-related adverse events (AEs) were fatigue (42.9%) and nausea (42.9%). Twelve (17.1%) patients experienced ≥1 fatal AE, one of which (asthenia) was treatment-related.

Conclusions: Although the azacitidine-epacadostat-pembrolizumab regimen was well tolerated, it was not associated with substantial clinical response in patients with advanced solid tumors previously exposed to immunotherapy.

Keywords

Humans, Azacitidine, Immune Checkpoint Inhibitors, Neoplasms, Interferons

Published Open-Access

yes

Recommended Citation

Luke, Jason J; Fakih, Marwan; Schneider, Charles; et al., "Phase I/II Sequencing Study of Azacitidine, Epacadostat, and Pembrolizumab in Advanced Solid Tumors" (2023). Faculty, Staff and Student Publications. 4870.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4870