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Original Investigation
November 5, 2020

Effect of Taxane Chemotherapy With or Without Indoximod in Metastatic Breast Cancer: A Randomized Clinical Trial

Author Affiliations
  • 1H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
  • 2University of Mississippi Cancer Center and Research Institute, Jackson
  • 3University of Virginia, Charlottesville
  • 4Cleveland Clinic, Cleveland, Ohio
  • 5Virginia Commonwealth University, Richmond
  • 6Wake Forest University, Winston-Salem, North Carolina
  • 7MD Anderson Cancer Center, Houston, Texas
  • 8NewLink Genetics Corporation, Ames, Iowa
  • 9University of Illinois at Chicago
  • 10Lankenau Institute for Medical Research, Wynnewood, Pennsylvania
JAMA Oncol. 2021;7(1):61-69. doi:10.1001/jamaoncol.2020.5572
Key Points

Question  Is the combination of indoximod and a taxane superior to a taxane alone in treating patients with ERBB2-negative metastatic breast cancer?

Findings  In this randomized clinical trial of 169 patients with ERBB2-negative metastatic breast cancer, the combination of indoximod and a taxane compared with a single-agent taxane resulted in neither superior clinical outcomes nor significantly greater toxic effects.

Meaning  Indoximod plus a taxane did not have superior efficacy compared with single-agent taxane in patients with metastatic ERBB2-negative breast cancer.


Importance  Indoleamine 2,3-dioxygenase 1 (IDO1) causes tumor immune suppression. The IDO1 pathway inhibitor indoximod combined with a taxane in patients with ERBB2-negative metastatic breast cancer was tested in a prospective clinical trial.

Objective  To assess clinical outcomes in patients with ERBB2-negative metastatic breast cancer treated with indoximod plus a taxane.

Design, Setting, and Participants  This phase 2 double-blinded randomized 1:1 placebo-controlled clinical trial enrolled patients at multiple international centers from August 26, 2013, to January 25, 2016. Eligibility criteria included ERBB2-negative metastatic breast cancer, ability to receive taxane therapy, good performance status, normal organ function, no previous immunotherapy use, and no autoimmune disease. The study was discontinued in June 2017 because of lack of efficacy. Data analysis was performed from February 2019 to April 2020.

Interventions  A taxane (paclitaxel [80 mg/m2] weekly 3 weeks on, 1 week off, or docetaxel [75 mg/m2] every 3 weeks) plus placebo or indoximod (1200 mg) orally twice daily as first-line treatment.

Main Outcomes and Measures  The primary end point was progression-free survival (PFS); secondary end points were median overall survival, objective response rate, and toxic effects. A sample size of 154 patients would detect a hazard ratio of 0.64 with 1-sided α = .1 and β = .2 after 95 events. Archival tumor tissue was stained with immunohistochemistry for IDO1 expression as an exploratory analysis.

Results  Of 209 patients enrolled, 169 were randomized and 164 were treated (85 in the indoximod arm; 79 in the placebo arm). The median (range) age was 58 (29-85) years; 166 (98.2%) were female, and 135 (79.9%) were White. The objective response rate was 40% and 37%, respectively (indoximod vs placebo) (P = .74). The median (range) follow-up time was 17.4 (0.1-39.4) months. The median PFS was 6.8 months (95% CI, 4.8-8.9) in the indoximod arm and 9.5 months (95% CI, 7.8-11.2) in the placebo arm (hazard ratio, 1.2; 95% CI, 0.8-1.8). Differences between the experimental and placebo arms in median PFS (6.8 vs 9.5 months) and overall survival (19.5 vs 20.6 months) were not statistically significant. Grade 3 or greater treatment-emergent adverse events occurred in 60% of patients in both arms.

Conclusions and Relevance  This randomized clinical trial found that, among patients with ERBB2-negative metastatic breast cancer, addition of indoximod to a taxane did not improve PFS compared with a taxane alone.

Trial Registration  ClinicalTrials.gov Identifier: NCT01792050

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