⁃ Patients with metastatic disease in the lung and/or liver, or soft tissue from any primary malignancy considered incurable by local therapies.

⁃ a. One prior anti-PD-1/L1 therapy allowed.

⁃ The target lesion(s) must be measurable as per irRECIST and repeated measurements at the same anatomical location should be achievable.

⁃ a. Participant must have at least 2 measurable lesions at screening. i. Abscopal cohort: At least one lesion will receive NBTXR3 and high dose radiation (high dose target lesion). The other lesion(s) (non-treated target lesion) will be followed for response and it will not receive NBTXR3 or RT.

⁃ ii. RadScopal™ cohort: At least one lesion will receive NBTXR3 and high dose radiation (high dose target lesion). The other lesion(s) will only receive low dose radiation (low dose target lesion).

⁃ Amenable to undergo the image guided (EBUS or CT or MRI) intratumoral injection of NBTXR3, in up to two (2) high dose target lesions, as determined by the investigator or treating physician at screening.

⁃ a. Intratumoral NBTXR3 injections only allowed in lung or liver lesions.

⁃ Selected high and low dose target lesions must be amenable to receive radiation therapy as determined by the investigator or treating radiation oncologist.

• Allowed high dose RT regimens are 50 Gy in 4 fractions or 60 Gy in 10 fractions

∙ Allowed low dose RT for RadScopal™ cohort is 1.4 Gy per fraction for 4 - 5 fractions to only low dose-target lesion(s) determined by the investigator or treating physician.

⁃ Patients can receive radiation therapy for symptomatic metastatic disease prior to enrollment or during the study a.

⁃ Age ≥ 18 years

⁃ Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

⁃ Laboratory Values at screening:

• Hemoglobin ≥ 9.0 g/dL

∙ Absolute Neutrophil Count (ANC) ≥ 1,500/mm3

∙ Platelet count ≥ 100,000/mm3

∙ Leukocytes ≥ 1500/mm3

∙ Creatinine ≤ 1.5 x upper limit of normal (ULN)

∙ Calc. creatinine clearance \> 30mL/min

∙ Total bilirubin ≤ 2.0 mg/dL

∙ AST / ALT ≤ 2.0 x upper limit of normal (ULN) or ≤ 3 x ULN for patients with liver metastases

⁃ For patients with lung metastases, adequate lung function with expiratory volume in 1 second (FEV1) ≥ 0.8L or ≥ 35% predicted and carbon monoxide diffusing capability (DLCO) ≥ 40% with or without bronchodilator within 30 days prior to NBTXR3 injection.

‣ Patients who meet the criterion above without oxygen (02), but need acute (started within 7 ± 3 days) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable.

‣ Negative urine or serum pregnancy test ≤ 7 days prior to NBTXR3 injection in all women of child-bearing potential (WOCBP). WOCBP must agree to follow instructions for method(s) of contraception for the duration the entire study period and 160 days (\

• 33 months) after the last dose of anti-PD-1/L-1 treatment. Local laws and regulations may require use of alternative and/or additional contraception methods. WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements but should still undergo pregnancy testing.

‣ Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.