Clinical Research Papers:

A first in man phase I trial of the oral immunomodulator, indoximod, combined with docetaxel in patients with metastatic solid tumors

Hatem H. Soliman _, Erica Jackson, Tony Neuger, Claire E. Dees, Donald R. Harvey, Hyo Han, Roohi Ismail-Khan, Susan Minton, Nicholas N. Vahanian, Charles Link, Daniel M. Sullivan and Scott Antonia

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Oncotarget. 2014; 5:8136-8146. https://doi.org/10.18632/oncotarget.2357

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Hatem H. Soliman1, Erica Jackson2, Tony Neuger1, E. Claire Dees3, R. Donald Harvey4, Hyo Han1, Roohi Ismail-Khan1, Susan Minton1, Nicholas N. Vahanian5, Charles Link5, Daniel M. Sullivan1, Scott Antonia1

1 H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

2 University of South Florida, Tampa, FL

3 University of North Carolina/Lineberger Cancer Center, Chapel Hill, NC

4 Winship Cancer Institute of Emory University, Atlanta, GA

5 NewLink Genetics Inc, Ames, IA

Correspondence to:

Dr. Hatem Soliman MD, e-mail: [email protected]

Keywords: Indoximod, 1-methyl-D-tryptophan, immunomodulator, docetaxel, indoleamine 2, 3 dioxygenase

Received: June 12, 2014     Accepted: August 16, 2014     Published: August 21, 2014


Background: Indoleamine 2,3-dioxygenase (IDO) is an enzyme that tumors use to create a state of immunosuppression. Indoximod is an IDO pathway inhibitor. Preclinical studies demonstrated that indoximod combined with chemotherapy was synergistic in a mouse model of breast cancer. A phase I 3+3 trial was designed to study the combination of docetaxel and indoximod.

Methods: Docetaxel was administered at 60 mg/m2 intravenously every 3 weeks dose levels 1-4 and 75 mg/m2 for dose level 5. Indoximod was given at 300, 600, 1000, 2000, and 1200 mg PO twice daily continuously for levels 1-5, respectively. Serum drug levels were measured.

Results: Twenty-seven patients were treated, with 22 evaluable for response. DLTs included grade 3 dehydration (level 1), hypotension(level 4), mucositis (level 4) and grade 5 enterocolitis (level 2). Dose level 5 is the recommended phase II dose. The most frequent adverse events were fatigue (58.6%), anemia (51.7%), hyperglycemia (48.3%), infection (44.8%), and nausea (41.4%). There were 4 partial responses (2 breast, 1 NSCLC, 1 thymic tumor). No drug-drug interactions were noted.

Conclusions: Docetaxel plus indoximod was well tolerated with no increase in expected toxicities or pharmacokinetic interactions. It was active in a pretreated population of patients with metastatic solid tumors.

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