Phase 1/2 study of epacadostat in combination with durvalumab in patients with metastatic solid tumors.
PD-1
durvalumab
epacadostat
kynurenine
neoplasms
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 01 2023
01 01 2023
Historique:
revised:
05
07
2022
received:
24
02
2022
accepted:
11
07
2022
pubmed:
31
10
2022
medline:
15
12
2022
entrez:
30
10
2022
Statut:
ppublish
Résumé
Targeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment. 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. 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. 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. A study of epacadostat (INCB024360) in combination with durvalumab (MEDI4736) in subjects with selected advanced solid tumors (ECHO-203) (NCT02318277).
Sections du résumé
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).
Identifiants
pubmed: 36309837
doi: 10.1002/cncr.34512
pmc: PMC10092291
doi:
Substances chimiques
epacadostat
71596A9R13
Oximes
0
Sulfonamides
0
Antibodies, Monoclonal
0
Banques de données
ClinicalTrials.gov
['NCT02318277']
Types de publication
Clinical Trial, Phase II
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-81Informations de copyright
© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
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