NCT05469490

Safety of Navoximod and NLG802 With Stereotactic Body Radiotherapy (SBRT) Treatment of Advanced Solid Tumors

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

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Luke, Jason, MD · Academic / Other
• Sex: All
• Age: 15 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Treatment for this trial will include stereotactic body radiation therapy (SBRT) to 1-4 metastases that can be safely irradiated, in combination with NLG802 and navoximod. The study will determine the safe doses of SBRT in combination with navoximod and NLG802 twice per day. The amount of SBRT administered will range from 30Gy to 50 Gy, depending upon the location of the tumor. If dose-limiting toxicities (DLT) are experienced, SBRT will be decreased accordingly. Disease assessment with computed tomography (CT) and/or magnetic resonance imaging (MRI if CT scan is contraindicated) will be performed in the screening period, after 8 weeks of starting SBRT/NLG802/navoximod and then every 8 weeks until progression of disease, at the completion of follow-up, or until participants withdraw from the study.

Conditions

• Advanced Solid Tumors

Interventions

Type	Name	Description
RADIATION	Stereotactic Body Radiotherapy (SBRT)	SBRT is specialize radiation that is effective for ablating tumors at primary and metastatic locations that increases antigen uptake/processing/presentation.
DRUG	navoximod	A small molecule inhibitor with potent inhibition of IDO1 enzymatic activity as shown both in vitro and in vivo. As the main function of IDO1 is the regulation of acquired immune tolerance, and its expression in tumor- and dendritic cells in tumor draining lymph nodes negatively correlates with cancer prognosis and survival, navoximod-mediated IDO1 inhibition may restore immune reactivity towards tumors.
DRUG	NLG802 (indoximod Prodrug)	An anti-tumor immunomodulator with the active ingredient of 1-methyl-D-tryptophan (NSC- 721782, 1-MT), which is an inhibitor of the indoleamine 2,3-dioxygenase (IDO) pathway that increases the bioavailability of indoximod by leveraging existing mechanisms of absorption, increasing the exposure of indoximod.

Timeline

• Start date: 2022-10-01
• Primary completion: 2024-08-01
• Completion: 2026-12-01
• First posted: 2022-07-21
• Last updated: 2022-09-30

Regulatory

• FDA-regulated drug study
• FDA-regulated device study