Phase 1/2 Study of Epacadostat in Combination With Durvalumab in Patients With Metastatic Solid Tumors

Authors

Aung Naing
Alain P Algazi
Gerald S Falchook
Benjamin C Creelan
John Powderly
Seth Rosen
Minal Barve
Niharika B Mettu
Pierre L Triozzi
John Hamm
Gongfu Zhou
Chris Walker
Zhiwan Dong
Manish R Patel

Publication Date

1-1-2023

Journal

Cancer

DOI

10.1002/cncr.34512

PMID

36309837

PMCID

PMC10092291

PubMedCentral® Posted Date

10-30-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Targeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment.

Methods: The open-label, phase 1/2 ECHO-203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti-PD-L1 monoclonal antibody in adult patients with advanced solid tumors.

Results: The most common treatment-related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)-naïve patients (16.1%) compared with patients who had received previous CPI (4.1%). Epacadostat pharmacodynamics were evaluated by comparing baseline kynurenine levels with those on therapy at various time points. Only the 300-mg epacadostat dose showed evidence of kynurenine modulation, albeit unsustained.

Conclusions: Epacadostat plus durvalumab was generally well tolerated in patients with advanced solid tumors. ORR was low, and evaluation of kynurenine concentration from baseline to cycle 2, day 1, and cycle 5, day 1, suggested >300 mg epacadostat twice daily is needed to ensure sufficient drug effect.

Clinical trial information: A study of epacadostat (INCB024360) in combination with durvalumab (MEDI4736) in subjects with selected advanced solid tumors (ECHO-203) (NCT02318277).

Keywords

Adult, Humans, Oximes, Sulfonamides, Antibodies, Monoclonal, Neoplasms, Neoplasms, Second Primary, Antineoplastic Combined Chemotherapy Protocols, durvalumab, epacadostat, kynurenine, neoplasms, PD‐1

Published Open-Access

yes

Recommended Citation

Naing, Aung; Algazi, Alain P; Falchook, Gerald S; et al., "Phase 1/2 Study of Epacadostat in Combination With Durvalumab in Patients With Metastatic Solid Tumors" (2023). Faculty, Staff and Student Publications. 4862.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4862