Navoximod

(GDC-0919, NLG919, RG6078)

Navoximod image: an investigational IDO1 inhibitor
Breast
  • Phase
  • I
  • II
  • III
Gastrointestinal
  • Phase
  • I
  • II
  • III
Genitourinary
  • Phase
  • I
  • II
  • III
Gynecologic
  • Phase
  • I
  • II
  • III
Hematologic
  • Phase
  • I
  • II
  • III
Lung
  • Phase
  • I
  • II
  • III
Melanoma
  • Phase
  • I
  • II
  • III
Solid Tumor
  • Phase
  • I
  • II
  • III

This compound and its uses are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in preclinical studies to humans is currently being evaluated.

Navoximod, an IDO1 inhibitor

Navoximod is an investigational, orally administered small molecule designed to selectively inhibit indoleamine 2,3-dioxygenase 1 (IDO1)—a rate-limiting catabolic enzyme involved in the conversion of tryptophan to kynurenine.1,2 Navoximod is designed to enhance, broaden, and/or sustain the antitumor immune responses triggered by complementary cancer treatment strategies, such as immune checkpoint blockade. The addition of navoximod to other cancer immunotherapies is hypothesized to overcome tumor-induced immune tolerance.3,4 In preclinical studies, navoximod was shown to inhibit processes involved in tumor immune escape.3

1 Navoximod (GDC-0919) is an investigational, orally administered small molecule inhibitor currently being studied for its potential to inhibit IDO1.1,2

Image: Tolerogenic state, Treg/MDSC activation and recruitment

2 Navoximod is designed to selectively inhibit IDO1 enzymatic activity, thereby inhibiting local tryptophan catabolism, which may reduce local kynurenine production within the tumor microenvironment.1,5

Image: Navoximod IDO1 inhibition, tryptophan inhibition, and kyurenine reduction

3 Preclinical data have shown that, in a murine-cell model, the addition of navoximod to an anti-PDL1 agent was associated with an increased ratio of CD8+ T cells to Tregs and enhanced antitumor activity.3 Navoximod continues to be investigated in ongoing clinical studies.

Image: Navoximod, immunogenic state, Treg/MDSC activation and recruitment

APC=antigen-presenting cell; CD8+=cluster of differentiation 8 positive; CTL=cytotoxic T lymphocyte; MDSC=myeloid-derived suppressor cell; NK=natural killer; PD-L1=programmed death-ligand 1; Treg=regulatory T cell.

References

  1. Platten M, von Knebel Doeberitz N, Oezen I, Wick W, Ochs K. Cancer immunotherapy by targeting IDO1/TDO and their downstream effectors. Front Immunol. 2015;5:673. doi:10.3389/fimmu.2014.00673. PMID: 25628622
  2. Munn DH, Mellor AL. IDO in the tumor microenvironment: inflammation, counter-regulation, and tolerance. Trends Immunol. 2016;37:193-207. PMID: 26839260
  3. Spahn J, Peng J, Lorenzana E, et al. Improved anti-tumor immunity and efficacy upon combination of the IDO1 inhibitor GDC-0919 with anti-PD-L1 blockade versus anti-PD-L1 alone in preclinical tumor models. J Immunother Cancer. 2015;3(Suppl2):P303.
  4. Nayak A, Hao Z, Sadek R, et al. Phase 1a study of the safety, pharmacokinetics, and pharmacodynamics of GDC-0919 in patients with recurrent/advanced solid tumors. Poster presented at: ESMO; September 25-29, 2015; Vienna, Austria.
  5. Mautino M, Jaipuri F, Waldo J, et al. NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. Poster presented at: AACR 104th Annual Meeting; April 6-10, 2013; Washington, DC. Poster 491.