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Phase 1/2 study of epacadostat in combination with durvalumab in patients with metastatic solid tumors

Aung Naing1, Alain P Algazi2, Gerald S Falchook3

  • 1MD Anderson Cancer Center, University of Texas, Houston, Texas, USA.

Cancer
|October 30, 2022
PubMed
Abstract

Insights

The combination of epacadostat and durvalumab showed a low objective response rate in advanced solid tumors. Higher doses of epacadostat may be needed for sufficient drug effect, with generally good tolerability observed.

Area of Science:

  • Oncology
  • Immunotherapy
  • Pharmacology

Background:

  • Targeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways offers a promising strategy for cancer treatment.
  • The IDO1 pathway plays a crucial role in immune suppression within the tumor microenvironment.

Purpose of the Study:

  • To evaluate the safety, tolerability, and efficacy of epacadostat, an IDO1 inhibitor, in combination with durvalumab, an anti-PD-L1 antibody.
  • To assess the impact of this combination therapy on advanced solid tumors in adult patients.

Main Methods:

  • An open-label, phase 1/2 clinical trial (ECHO-203) was conducted.
  • The study enrolled adult patients with advanced solid tumors.
  • Safety, tolerability, efficacy, and pharmacodynamics (kynurenine levels) were assessed.

Main Results:

  • The most frequent treatment-related adverse events included fatigue, nausea, decreased appetite, pruritus, rash, and diarrhea.
  • The overall objective response rate (ORR) was 12.0%, with a higher ORR of 16.1% in patients who had not previously received immune checkpoint inhibitors (CPI).
  • Kynurenine modulation was observed only at the 300-mg epacadostat dose, and this effect was not sustained.

Conclusions:

  • Epacadostat plus durvalumab was generally well-tolerated in patients with advanced solid tumors.
  • The observed ORR was low, suggesting that higher doses of epacadostat (e.g., >300 mg twice daily) may be necessary to achieve a sufficient therapeutic effect.
  • Further investigation into optimal dosing is warranted to maximize the potential benefits of this combination therapy.
Keywords:
PD-1durvalumabepacadostatkynurenineneoplasms

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