Nicholas N. Vahanian

Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

Yousef Zakharia, Robert R. McWilliams, Olivier Rixe, Joseph J. Drabick et autres

BACKGROUND: The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) …

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

Daniel M. Sullivan, Roohi R. Ismail-Khan, Hatem Hussein Soliman, Scott Joseph Antonia et autres

BackgroundIndoleamine 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 …

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Effect of Taxane Chemotherapy With or Without Indoximod in Metastatic Breast Cancer

Veronica Mariotti, Hyo Sook Han, Roohi R. Ismail-Khan, Shou‐Ching Tang et autres

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 …

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Indoximod opposes the immunosuppressive effects mediated by IDO and TDO via modulation of AhR function and activation of mTORC1

Erik L. Brincks, James Truslow Adams, Lifu Wang, Benjamin A. Turner et autres

// Erik L. Brincks 1 , 2 , James Adams 1 , Lifu Wang 1 , Benjamin Turner 1 , Agnieszka Marcinowicz 1 , Jiyuan Ke 1 , Michael Essmann 1 , Lucía M. Mautino 1 , Clarissa Van Allen 1 , …

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Discovery of indoximod prodrugs and characterization of clinical candidate NLG802

Sanjeev Kumar, Firoz Ali Jaipuri, Jesse P. Waldo, Hima Potturi et autres

A series of different prodrugs of indoximod, including estesrs and peptide amides were synthesized with the aim of improving its oral bioavailability in humans. The pharmacokinetics of prodrugs that were stable in buffers, plasma and simulated gastric and intestinal fluids was first …

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Results of the NLG2105 Phase I Trial Using the IDO Pathway Inhibitor Indoximod, in Combination with Radiation and Chemotherapy, for Children with Newly Diagnosed DIPG

Theodore S. Johnson, Dolly G. Aguilera, Ahmad K. Al-Basheer, Zuzana Berrong et autres

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A Phase I Study of Alpha-1,3-Galactosyltransferase-Expressing Allogeneic Renal Cell Carcinoma Immunotherapy in Patients with Refractory Metastatic Renal Cell Carcinoma

Andrew Warren Hahn, Charles G. Drake, Samuel Ray Denmeade, Yousef Zakharia et autres

LESSONS LEARNED: HyperAcute Renal immunotherapy was well tolerated and demonstrated antitumor activity in patients requiring salvage-line treatment for metastatic renal cell carcinoma (mRCC). HyperAcute Renal immunotherapy was safely administered with concomitant salvage-line treatments for mRCC, and it may be a candidate for …

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Abstract CT151: A Phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer

Linda Duska, David M. O’Malley, Carolyn N. Krasner, Russell J. Schilder et autres

Abstract Background: NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone linked to camptothecin, a topoisomerase-1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. …

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Abstract CT151: A Phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer

Linda Duska, David M. O’Malley, Carolyn N. Krasner, Russell J. Schilder et autres

Background: NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone linked to camptothecin, a topoisomerase-1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. The …

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Efficacy of alpha-1,3-galactosyltransferase-expressing allogeneic renal cell carcinoma immunotherapy in patients (pts) with refractory metastatic renal cell carcinoma (mRCC).

Andrew Warren Hahn, Charles G. Drake, Samuel Ray Denmeade, Yousef Zakharia et autres

590 Background: HyperAcute Renal (HAR) immunotherapy consists of two allogeneic renal cancer cell lines that have been genetically modified to express α(1,3)Gal, to which humans have an inherent pre-existing immunity. A previous report demonstrated that HAR is well tolerated in pts with …

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Abstract 3753: Indoximod modulates AhR-driven transcription of genes that control immune function

Erik L. Brincks, James Truslow Adams, Michael Essmann, Benjamin A. Turner et autres

Abstract The IDO pathway mediates immunosuppressive effects by metabolizing tryptophan (Trp) into kynurenine (Kyn). The depletion of Trp stimulates downstream signaling through nutrient sensors GCN2 and mTOR, while the production of Kyn stimulates signaling through the aryl-hydrocarbon receptor (AHR) transcription factor. The …

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Phase Ia study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) in patients with recurrent advanced solid tumors

Asha Nayak-Kapoor, Zhonglin Hao, Ramses Sadek, Robin Dobbins et autres

Background Indoleamine-2,3-dioxygenase 1 (IDO1) catalyzes the oxidation of tryptophan into kynurenine and is partially responsible for acquired immune tolerance associated with cancer. The IDO1 small molecule inhibitor navoximod (GDC-0919, NLG-919) is active as a combination therapy in multiple tumor models. Methods This …

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