Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors

Luke, JJ; Fakih, M; Schneider, C; Chiorean, EG; Bendell, J; Kristeleit, R; Kurzrock, R; Blagden, SP; Brana, I; Goff, LW; O’Hayer, K; Geschwindt, R; Smith, M; Zhou, F; Naing, A

Journal article

Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors

Abstract:: Cancer epigenetics; Cancer immunotherapyEpigenética del cáncer; Inmunoterapia contra el cáncerEpigenètica del càncer; Immunoteràpia del càncerBackground 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.This study was sponsored by Incyte Corporation

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Luke, J. J., Fakih, M., Schneider, C., Chiorean, E. G., Bendell, J., Kristeleit, R., Kurzrock, R., Blagden, S. P., Brana, I., Goff, L. W., O’Hayer, K., Geschwindt, R., Smith, M., Zhou, F., & Naing, A. (2023). Phase I/II sequencing study of azacitidine, epacadostat, and pembrolizumab in advanced solid tumors. British Journal of Cancer, 128(12), 2227–2235.

MLA Style

Luke, JJ, et al. “Phase I/II Sequencing Study of Azacitidine, Epacadostat, and Pembrolizumab in Advanced Solid Tumors.” British Journal of Cancer, vol. 128, no. 12, 2023, pp. 2227–35.

Chicago Style

Luke, JJ, M Fakih, C Schneider, et al. 2023. “Phase I/II Sequencing Study of Azacitidine, Epacadostat, and Pembrolizumab in Advanced Solid Tumors.” British Journal of Cancer 128 (12): 2227–35.
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