NBTXR3 Activated by Radiotherapy for Patients With Advanced Cancers Treated With An Anti-PD-1 Therapy

Inclusion Criteria

• •Signed informed consent form
• •Biopsy-confirmed cancer diagnosis indicated to receive anti-PD-1 therapy:
• •Dose Escalation:
• •1. Escalation Cohort 1: Is inoperable LRR with tumor in previously irradiated HN field that is amenable to re-irradiation or R/M HNSCC with tumor in previously irradiated HN field that is amenable to re-irradiation, or
• •2. Escalation Cohort 2: Has metastasized to the lung (including involved lymph nodes) with tumor in a previously non-irradiated lung field, or
• •3. Escalation Cohort 3: Has metastasized to the liver with tumor in a previously non-irradiated liver field
• •Expansion:
• •1. Expansion Cohorts 1 and 2: Is inoperable LRR or R/M HNSCC with at least one lesion that is amenable to irradiation within head and neck region, lung or liver
• •2. Expansion Cohort 3: Is inoperable NSCLC, malignant melanoma, HCC, RCC, urothelial cancer, cervical cancer, TNBC that has metastasized to soft tissues, lung (including mediastinal lymph nodes) or liver with at least one lesion that is amenable to irradiation
• •* Prior anti-PD-1 exposure as follows:
• •Dose Escalation (all cohorts):
• •1. Has not received prior anti-PD-1 therapy (i.e., anti-PD-1 naïve), or
• •2. Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 primary resistance (i.e., primary anti-PD-1 non-responder), or
• •3. Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 secondary resistance (i.e., secondary anti-PD-1 non-responder)
• •Expansion:
• •1. Expansion Cohorts 1 and 3: Has received prior anti-PD-1 therapy and meets criteria consistent with anti-PD-1 primary or secondary resistance as described above
• •2. Expansion Cohort 2: Has not received prior anti-PD-1 therapy (i.e., anti-PD-1 naïve)
• •* Has at least one tumor lesion that can be accurately measured according to RECIST 1.1. and is amenable for intratumoral injection
• •* ECOG performance status 0-2
• •* Life expectancy \>12 weeks
• •* Adequate organ and bone marrow function
• •* Negative pregnancy test ≤ 7 days prior to NBTXR3 injection in all female participants of child-bearing potential