Phase I Study Investigating the Safety of Navoximod and NLG802 in Combination With Stereotactic Body Radiotherapy (SBRT) in Subjects With Advanced Solid Tumors

This early phase trial proposes to study of stereotactic body radiation therapy (SBRT) with navoximod and NLG802, a prodrug of indoximod. Combinations of immune-oncology (IO) agents with complementary mechanisms as well as radiation represent a promising strategy to improve response rates to immunotherapy. Radiation therapy induces immunogenic cell death, increases production of tumor specific antigens, enhances TH cell functioning, and modulates immunosuppressive cell populations such as T regulatory cells and myeloid derived suppressor cells.

Start Date01 Oct 2022

Sponsor / Collaborator

Lumos Pharma, Inc.

JPRN-jRCT2080223275

Phase 1

PHASE I STUDY OF GDC-0919 AS A SINGLE AGENT AND IN COMBINATION WITH OTHER ANTICANCER DRUGS IN PATIENTS WITH ADVANCED SOLID TUMORS

Start Date01 Jun 2016

Sponsor / Collaborator

Chugai Pharmaceutical Co., Ltd.

NCT02471846

/ CompletedPhase 1

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0919 Administered With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of GDC-0919 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy or for which standard therapy is ineffective, intolerable, or inappropriate. Participants will be enrolled in two stages, including a dose-escalation stage and an expansion stage.

Start Date28 Jul 2015

Sponsor / Collaborator

Genentech, Inc.

100 Clinical Results associated with Navoximod

100 Translational Medicine associated with Navoximod

100 Patents (Medical) associated with Navoximod

146

Literatures (Medical) associated with Navoximod

01 Aug 2026·Biomaterials advances

Synergistic photodynamic therapy and IDO inhibition via a self-assembled nanomedicine potentiates PD-L1 blockade in gastrointestinal cancers

Article

Author: Zheng, Chen ; Feng, Xianquan ; Lin, Yun ; Zhang, Qi ; Li, Dongliang ; Yang, Zhirong ; Zhang, Yan ; Liang, Pingping ; Chen, Xi ; Wu, Jingjing

Tumor metastasis remains a major obstacle to achieving favorable prognosis and quality of life in patients with gastrointestinal cancers. Although immune checkpoint blockade (ICB) has shown potential in reducing metastatic risk, its efficacy largely depends on sufficient tumor-infiltrating T lymphocytes. Here, we developed a self-assembled nanomedicine (VN NPs) co-loaded with verteporfin and the IDO-1 inhibitor NLG919, using TPGS as a stabilizer and long-circulating agent. Upon intravenous administration, VN NPs preferentially accumulated in tumor tissue through passive targeting. Under light irradiation, verteporfin-induced photodynamic therapy triggered immunogenic cell death, promoted dendritic cell maturation, and initiated a systemic anti-tumor immune response. Simultaneously, NLG919 potently inhibited IDO-1 activity, blocking the conversion of tryptophan to kynurenine, thereby reversing local immunosuppression and synergizing with photodynamic immunotherapy. In murine models of gastric and colon cancer, this combination strategy not only suppressed primary tumor growth but also significantly inhibited distant metastasis in colon cancer. This simple yet effective nanoplatform amplifies ICB efficacy and represents a promising translational approach for metastatic gastrointestinal malignancies.

01 Jul 2026·Journal of Advanced Research

Akkermansia muciniphila-derived postbiotics reprogram immune balance to combat sepsis via the IDO1/Kyn/AhR metabolic axis

Article

Author: Wang, Liangliang ; Yin, Ruopeng ; Zhang, Yuting ; Dong, Wang ; Dai, Huanqin ; Bi, Yanliang ; Sun, Li ; Wang, Tao ; Sun, Jingzu ; Liu, Hongwei

INTRODUCTION:

Sepsis is a life-threatening syndrome of organ dysfunction driven by a dysregulated immune response. Effective therapeutic strategies to restore immune homeostasis remain limited. Hypoacylated lipooligosaccharides (ALOS) from Akkermansia muciniphila have emerged as potential immunomodulatory postbiotics, yet their therapeutic potential in sepsis and the underlying mechanisms remain unexplored.

OBJECTIVES:

This study aims to investigate whether ALOS confers protection in experimental models of sepsis induced by toxic lipopolysaccharides (LPS) or cecal ligation and puncture (CLP), and the mechanism by which ALOS exerts its anti-inflammatory and regulatory effects.

METHODS:

In LPS or CLP-induced mouse sepsis models and a porcine sepsis model, ALOS (0.2 mg/kg, i.p.) was administered once every two days before challenge or half an hour post-surgery. Survival rates, physiological and biochemical parameters were assessed. Based on 16S rRNA gene amplicon sequencing and barrier function assessment, the changes of the colonic microbiota and metabolites and anti-inflammatory capacity were analyzed. The anti-inflammatory and immunomodulatory mechanisms of ALOS were investigated through dendritic cell phenotyping, transcriptomic analysis, inhibitor assays, and conditioned medium experiments. Finally, the safety of ALOS was evaluated in C57BL/6J mice following one-week administration (0.2 mg/kg, i.p.).

RESULTS:

ALOS pretreatment significantly suppresses sepsis, reduces the proportion of pro-inflammatory Th17 cells, and increases regulatory T cells (Treg). Mechanistically, ALOS induced semi‑mature dendritic cells with upregulated IDO1 expression, leading to enhanced production of kynurenine (Kyn). Kyn activated the aryl hydrocarbon receptor (AhR) to drive Treg differentiation. The protective effect of ALOS was completely reversed by NLG919, whereas Kyn administration mimicked the therapeutic benefit. ALOS also produced therapeutic protection on sepsis. In a porcine sepsis model, pretreatment of ALOS exerted systemic anti‑inflammatory effects and protected multiple organs.

CONCLUSION:

This study highlights the protective role of ALOS in sepsis and identifies the IDO1-Kyn-AhR immune axis as the major underlying mechanism.

01 May 2026·JOURNAL OF CONTROLLED RELEASE

Carrier-free nanoreshapers disrupt cancer-associated fibroblast barriers and alleviate immunosuppression for synergistically potentiated immunotherapy

Article

Author: Wang, Xuechun ; Zhao, Wen ; Ma, Zilin ; Yue, Yi ; Li, Songyan ; Song, Cong ; Du, Jintao ; Liu, Binghan ; Zhang, Guiqiang ; Wei, Yuhua

The dense extracellular matrix and immunosuppressive microenvironments create dual physical and immunological barriers that often render immunotherapy ineffective in solid tumors. Herein, by using a one-pot approach, we developed a carrier-free nanoreshaper (QN NP) through coordinating manganese ions (Mn²⁺) with quercetin (Qc) and the indoleamine 2,3-dioxygenase 1 inhibitor NLG919 to lift these restrictions. Benefiting from uniform size and exceptional stability, QN NPs achieved efficient tumor accumulation, and triggered drug release in response to tumor microenvironment. As active pharmaceutical ingredients, Qc normalizes cancer-associated fibroblasts and reduces extracellular matrix deposition; Mn²⁺ triggers potent immune responses both by generating hydroxyl radicals to induce immunogenic cell death and by activating the stimulator of interferon genes (STING) pathway; and NLG919 disrupts the tryptophan/kynurenine metabolic pathway to alleviate tumor immunosuppression. Together, the coordinated action overcomes both the physical barrier and immunosuppressive niche, thereby enhancing immune cell infiltration and effector function. Furthermore, combining QN NPs with an anti-PD-L1 antibody generated robust synergistic activity, leading to cooperative suppression of both primary tumor growth and pulmonary metastases. This carrier-free nanoreshaping strategy overcomes the dual challenges of stromal fibrosis and immune evasion, providing a promising paradigm for developing combined immunotherapies based on physical barrier disruption and microenvironment reprogramming.

News (Medical) associated with Navoximod

07 Nov 2017

·www.biospace.com

Confident Bristol-Myers to Launch 700-Patient Phase III IDO Trial for Melanoma

Bristol-Myers is initiating a Phase III clinical trial of BMS-986205 with nivolumab in patients with advanced melanoma. Bristol-Myers Squibb Company is initiating a Phase III clinical trial of BMS-986205 with nivolumab in patients with advanced melanoma. Although the trial is not yet open, it has been announced on the ClinicalTrials.gov website. The compound, BMS-986205, is a IDO1 inhibitor. Nivolumab is the company’s powerful cancer drug, Opdivo. IDO inhibitors are a new class of cancer drugs, although the research on them is fairly new, so not much is known about them, including if they work. And there appears to be some concern that they don’t, although Bristol-Myers’ launch of a trial in this case suggests they, at least, think they do. Stat writes , “The next incremental answer to that question is coming this week, when Bristol-Myers Squibb will present early-stage data on a combination of its IDO drug and the multibillion-dollar cancer-killer called Opdivo. The results, known only to Bristol and its collaborators right now, were apparently positive enough to convince the company to launch a 700-patient Phase III trial, testing the combination against advanced melanoma.” Stat argues that the data must be significant, given that Phase III clinical trials are expensive and high-risk. Both Merck and Incyte are running similar trials with Keytruda and a different IDO inhibitor, with a data readout expected in the first half of 2018. “And thus if Bristol had concerns about the overarching idea, it could simply wait to see its competitors’ results. The fact that the company is wasting literally no time suggests Bristol is convinced IDO is for real.” The trial, according to the ClinicalTrials.gove website, “is to see if BMS-096205 combined with nivolumab, compared to nivolumab by itself, is more effective in treating melanoma that has spread or is unable to be removed by surgery, and has not previously been treated.” Back in April, Bristol-Myers’ oncology development head, Faoud Namouni, told Endpoints News ’ John Carroll, “It seems our IDO has the potential to be one of the most potent in the class.” Perhaps clouding the issue is a failed IDO inhibitor trial with Genentech ’ s Tecentriq and NewLink Genetics ’ IDO inhibitor indoximod , which resulted in Genentech turning the rights to the drug back. Derek Lowe, writing for Science Translational Medicine, said, “Something’s wrong, but what? Incyte is developing an IDO inhibitor of their own (epacadostat) and combining it with Merck’s Keytruda is providing the results that one would hope for. So the mechanism is likely to be sound. Complicating the picture, though, is that the Roche/Genentech PD-L1 antibody used in this study (Tecentriq, atezolizumab) had a recent unexpected failure in bladder cancer. It will be tempting for NewLink (and their investors) to think that the antibody was the problem, but there’s just not enough evidence to make that case one way or another. NewLink itself is under a lot of pressure after they’ve had disappointing results with their other IDO inhibitor, indiximod, in breast cancer, and it might be tough to round up another partner at this point. There’s a fair chance that we may never find out why GDC-0919 did what it did, but I hope that we eventually get some idea.”

Phase 3

08 Jun 2017

·www.biospace.com

NewLink Genetics Stock Plunges After Genentech Bails on $1 Billion+ IDO Deal

June 8, 2017 By Mark Terry , BioSpace.com Breaking News Staff Ames, Iowa – NewLink Genetics announced that Genentech was returning the rights to its IDO inhibitor GDC-0919 (navoximod). However, the overall research collaboration the two companies have to identify the next generation IDO/TDO (tryptophan 2,3-dioxygenase) inhibitors will continue. The original deal had an upfront payment of $150 million and with milestones, could have hit over $1 billion. The deal was inked in October 2014. NewLink licensed GDC-0919, which was then called NLG919, to Roche/Genentech . Genetic Engineering & Biotechnology News writes , “The companies reasoned that targeting the IDO and TDO pathways represented a breakthrough approach to fighting cancer, citing earlier studies showing that the IDO pathway was active both within tumor cells as a direct defense against T-cell attack, and within antigen presenting cells in tumor-draining lymph nodes.” John Carroll, writing for Endpoints News , says, “This is the latest in a series of gut punches to NewLink, which was sent reeling last year and was forced to restructure in the wake of the failure of its pancreatic cancer vaccine. IDO, a hot ticket in biotech now with Incyte evidently well in the lead, was supposed to be its path back.” It was only a week ago that NewLink announced that its Phase II trial of indoximod plus taxane chemotherapy, either docetaxel or paclitaxel, did not meet its primary endpoints. The endpoints were a statistically significant difference in progression-free survival versus placebo plus taxane chemotherapy in metastatic breast cancer. “We are obviously disappointed in this decision,” said Charles Link , NewLink Genetics’ chief executive officer, in a statement. “We remain committed to advancing our IDO pathway inhibitor indoximod, which continues to generate exciting data in combination with anti-PD-1 agents, cancer vaccines, and chemotherapy in multiple cancer types including melanoma, prostate cancer, acute myeloid leukemia, and pancreatic cancer.” NewLink Genetics , which had been trending downward since March, took a hard hit and is currently trading for $10.62. Shares traded on March 31 for $24.10, dropped to $15.50 on April 13, climbed back to $19.05 on April 26 before beginning a strong drop. This drop follows only a few days after Michael Uln , an analyst with Baird, gave the stock an “Outperform” rating and a price target of $25 after hosting an investor lunch at ASCO in Chicago. At that time, Baird suggested that the IDO pipeline was underappreciated. Carroll writes, “The writing, though, was on the wall when investigators reported that GDC-0919 delivered only a 10 percent overall response rate in all tumor types in a combination study with Tecentriq—a PD-L1 checkpoint that is also under a cloud since the big Phase III failure in bladder cancer. Genentech is not known for pursuing futile work in cancer.” At one point in April, the idea of Gilead Sciences acquiring NewLink Genetics was floated. Generally, the top suggestion has been Incyte Corporation , at least until its baricitinib for rheumatoid arthritis was rejected by the U.S. Food and Drug Administration (FDA) . The rationale for NewLink was promising interim results from a Phase II trial of indoximod in combination with checkpoint inhibitors to treat advanced melanoma. Incyte’s epacadostat is an IDO inhibitor, and so is NewLink’s indoximod and GDC-0919. But NewLink is a lot less expensive than Incyte—even more so now. Todd Campbell, writing for The Motley Fool in April, said, “Despite the solid showing (of indoximod), many industry watchers believe that apacadostat delivers a better blend of efficacy and safety because it targets IDO directly. Unlike apacadostat, indoximod disables IDO via cell signaling.” But, depending on what NewLink plans to do with their newly reacquired IDO inhibitor, it may be a moot point.

VaccinePhase 2License out/inPhase 3

22 May 2017

·www.biospace.com

6 (Plus 2!) Most Notable ASCO Abstracts So Far

May 22, 2017 By Mark Terry , BioSpace.com Breaking News Staff The American Society of Clinical Oncology (ASCO) meeting is being held in Chicago from June 2 through 6. In preparation, most companies and researchers have already submitted abstracts of presentations and posters, giving everyone interested, including investors, an advanced look at the data. Shanthi Rexaline , writing for Benzinga , takes a look at six notable abstracts—so far. 1. NewLink Genetics Based in Ames, Iowa, NewLink Genetics is presenting data from two clinical trials of its IDO pathway inhibitors, indoximod and navoximod, that are being evaluated in combination therapeutics in multiple solid tumors. GDC-0919 is being tested in a Phase Ib trial with Genentech ’s Tecentriq. Indoximod is being evaluated with Dendreon ’s Provenge in a Phase II trial in patients with metastatic castration resistant prostate cancer. NewLink Genetics is currently trading for $14.78. 2. Incyte Corporation Headquartered in Wilmington, Del., Incyte Corporation is presenting data from its Phase I/II ECHO-204 clinical trial of epacadostat in combination with Bristol-Myers Squibb ’s Opdivo in patients with squamous cell carcinoma of the head and neck (SCCHN), melanoma (MEL), ovarian cancer (OVC), and colorectal cancer (CRC). Rexaline notes that, “New data to be presented by Incyte showed that Epacadostat in combination with Merck & Co ’s PD-1 therapy Keytruda was well tolerated and demonstrated durable clinical responses across multiple solid tumor.” Incyte is currently trading for $131.43. 3. Merus NV Based in Utrecht, the Netherlands, Merus NV will present the results of its first-in-human Phase I/II trial of MCLA-128 in solid tumors, as well as final Phase I data in HER2-positive metastatic breast cancer (MBC) from the Phase II part of the trial. MCLA-127 is designed to block HER3-heregulin-dependent tumor growth and survival in addition to enhancing immune-mediated cytotoxicity in tumors.” Merus is currently trading for $19.78. 4. Syndax Pharmaceuticals Headquartered in Waltham, Mass., Syndax Pharmaceuticals is presenting data fron the ongoing Phase II ENCORE 601 trial of entinostat in combination with Merck’s Keytruda in multiple cancer indications. The poster is titled, “ENCORE 601: A Phase II study of entinostat (ENT) in combination with pembrolizumab (PEMBRO) in patients with melanoma.” Syndax is currently trading for $14.34. 5. CytRx Corporation Based in Los Angeles, Calif., CytRx Corporation is presenting two abstracts, one in an oral presesntation. The first is an update from its Phase III trial of aldoxorubicin versus the investigator’s choice in patients with relapsed and refractory soft tissue sarcomas (STS). The second presentation, a poster, is an update of an ongoing Phase I/II clinical trial combining aldoxorubicin with ifosfamide/mesna (I-M) in first- and second-line soft tissue sarcomas. “In addition to the significantly prolonged progression-free survival achieved by both North American and L-sarcoma patients, the data presented at ASCO this year demonstrate that, unlike any other drugs in this class, aldoxorubicin can be dosed continuously with minimal to no cardiotoxicity,” said Sant Chawla , director of the Sarcoma Oncology Center in Santa Monica, Calif., and principal investigator for the Phase III trial, in a statement. “Another distinct advantage is its ability to be administered to patients who have already been treated with doxorubicin. Taken together, these findings support aldoxorubicin’s potential as a superior anthracycline treatment for patients suffering with these highly complex and difficult to treat types of cancer.” CytRX is currently trading for $0.52. 6. ESSA Pharma Headquartered in Vancouver, Canada, ESSA Pharma is presenting data from the Phase I part of its ongoing Phase I/II clinical trial of EPI-506 in prostate cancer. Abstract 5032 is titled, “Efficacy, safety, tolerability and pharmacokinetics of EPI-506 (ralaniten acetate), a novel androgen receptor (AR) N-terminal domain (NTD) inhibitor, in men with metastatic castration resistant prostate cancer (ImCRPC) progressing after enzalutamide and/or abiraterone.” ESSA is currently trading for $2.29. Rexaline also offers up to other companies, Leap Therapeutics , which is releasing positive interim data from a Phase I trial of DKN-01 in combination with chemotherapy for advanced biliary tract cancers, and ImmunoGen , which is presenting top-line data from a Phase I trial of mirvetuximab soravtansine in ovarian cancer.

Phase 1ASCOPhase 2Phase 3Clinical Result

100 Deals associated with Navoximod

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endometrial Carcinoma	Phase 1	United States	Genentech, Inc.	28 Jul 2015
Endometrial Carcinoma	Phase 1	France	Genentech, Inc.	28 Jul 2015
Endometrial Carcinoma	Phase 1	South Korea	Genentech, Inc.	28 Jul 2015
Endometrial Carcinoma	Phase 1	Spain	Genentech, Inc.	28 Jul 2015
Melanoma	Phase 1	United States	Genentech, Inc.	28 Jul 2015
Melanoma	Phase 1	France	Genentech, Inc.	28 Jul 2015
Melanoma	Phase 1	South Korea	Genentech, Inc.	28 Jul 2015
Melanoma	Phase 1	Spain	Genentech, Inc.	28 Jul 2015
Non-Small Cell Lung Cancer	Phase 1	United States	Genentech, Inc.	28 Jul 2015
Non-Small Cell Lung Cancer	Phase 1	France	Genentech, Inc.	28 Jul 2015

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02471846 (Pubmed \| Clin Cancer Res) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	157	Navoximod +Atezolizumab	ndljnkjlty(bioycfysds) = fatigue 22%, rash 22%, and chromaturia 20% yekvswbahu (vvfacompdi )	Positive	01 Jun 2019
NCT02048709 (Pubmed \| J Immunother Cancer) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	22	GDC-0919	xnfzxnzwqo(yuhkqaqrcm) = kzugcloxfc kcbyuzoroo (oprislbohk ) View more	Positive	20 Jun 2018
NCT02471846 (ASCO 12017 \| ASCO 22017) Manual	Phase 1	Solid tumor	52	GDC-0919+Atezolizumab	hxnbldnacq(tzqxooazlc) = ogvptotwmi vatninzchm (wvrmrnlbcp ) View more	Positive	04 Jun 2017

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