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Oncotarget. 2018 Jan 10;9(11):10110-10117. doi: 10.18632/oncotarget.24118. eCollection 2018 Feb 9.

A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer.

Author information

1
Breast Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
2
Immunology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
3
Anatomic Pathology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
4
Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
5
Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Abstract

Background:

Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted.

Materials and Methods:

The phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks. Primary endpoints were maximum-tolerated dose in phase 1 and objective response in phase 2. Flow cytometry measured immune responses.

Results:

Thirty-nine patients were treated. In combination with Ad.p53-DC vaccine, the maximum-tolerated dose of indoximod was 1600 mg twice daily. Attributable toxicities were grade 1-2. Best response was stable disease in 4 patients. Immunologic responses were detected in 7 out of 23 evaluable patients. Median progression-free survival was 13.3 weeks (95% confidence interval, 12.97-21.85) and median overall survival was 20.71 weeks (95% confidence interval, 25.75-46.15). Nine out of 22 patients (40%) benefitted from chemotherapy after vaccination. Median overall survival in chemotherapy responders was 69.4 weeks (30.1-122.1).

Conclusions:

Indoximod 1600 mg twice daily with Ad.p53-DC was well tolerated. There may have been a chemosensitization effect. Future trials should explore combining this treatment with chemotherapy.

KEYWORDS:

adenovirus-p53 transduced dendritic cell vaccine; cancer vaccine; immunotherapy; indoleamine 2,3-dioxygenase; indoximod

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