Phase I/II Randomized Study of NBTXR3 Activated by Abscopal or RadScopal Radiation in Combination With Immunotherapy (Anti-PD-1/L-1) for Patients With Advanced Solid Malignancies

Primary Objective Phase I \& II • To evaluate efficacy and safety of NBTXR3 activated by radiation (Abscopal or RadScopal™) in combination with immunotherapy ( anti-PD-1/L-1) Secondary Objective: * To evaluate the safety profile of NBTXR3 activated by radiation (Abscopal or RadScopal™) in combination with immunotherapy ( anti-PD-1/L-1). * To evaluate time-to-event outcomes of NBTXR3 activated by radiation (Abscopal or RadScopal™) in combination with immunotherapy ( anti-PD-1/L-1). Exploratory Objectives: I. To evaluate radiomic measurements with outcomes of study treatments. II. To evaluate biomarkers of response in subjects after receiving study treatment. OUTLINE: Patients are randomized to 1 of 2 cohorts. COHORT I: Patients receive NBTXR3 intratumorally on day 1. Patients also receive ( anti-PD-1/L-1) intravenously (IV) on day 8. Beginning day 15, patients undergo Abscopal radiation therapy over 1-2 weeks. Cycles with ( anti-PD-1/L-1) repeat every 3-6 weeks per standard of care up to 2 years in the absence of disease progression or unacceptable toxicity. COHORT II: Patients receive NBTXR3 intratumorally on day 1. Patients also receive ( anti-PD-1/L-1) IV on day 8. Beginning day 15, patients undergo RadScopal radiation therapy over 1-2 weeks. Cycles with ( anti-PD-1/L-1)repeat every 3-6 weeks per standard of care up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for up to 2 years post-radiation therapy.