Clinical Research Papers:
A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer
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Hatem Soliman1,2, Fatema Khambati2, Hyo S. Han1, Roohi Ismail-Khan1, Marilyn M. Bui3, Daniel M. Sullivan4 and Scott Antonia2,5
1Breast Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
2Immunology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
3Anatomic Pathology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
4Malignant Hematology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
5Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Hatem Soliman, email: [email protected]
Keywords: indoximod; adenovirus-p53 transduced dendritic cell vaccine; cancer vaccine; immunotherapy; indoleamine 2,3-dioxygenase
Received: October 03, 2017 Accepted: November 28, 2017 Published: January 10, 2018
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.
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