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.
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.