177Lu-DOTA-EB-TATE in Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors

Exclusion Criteria

• •Women who are pregnant or breastfeeding
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-DOTA-EB-TATE as assessed from medical records
• •Previous treatment with more than 4 cycles of 177Lu-DOTA-TATE
• •Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 4 weeks or 4 half-lives whichever is longer, before the first administration of study drug.
• •Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 3 months after the last dose of study drug.
• •Life expectancy \< 6 months as assessed by the treating physician
• •\> 80% liver involvement by tumor
• •\> 25% bone marrow involvement by tumor
• •Poorly differentiated neuroendocrine neoplasms, such as poorly differentiated neuroendocrine carcinoma, small- and large-cell neuroendocrine carcinoma; mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN); Grade 3 neuroendocrine carcinomas (NEC)
• •Presence of somatostatin receptor negative lesions if they cannot be addressed with loco-regional therapies prior to the treatment start
• •Deteriorated renal function, as indicated by a serum creatinine clearance \> 1.7 mg/dL
• •Deteriorated bone marrow function
• •Deteriorated liver function
• •Toxicities from prior therapies that have not resolved to grade 1 or grade 0
• •Active and clinically significant bacterial, fungal, or viral infection, including hepatitis B (HBV), hepatitis C (HBC), know human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness
• •Known brain metastases and/or carcinomatous meningitis, unless these metastases have been treated and stabilized
• •Uncontrolled diabetes mellitus as defined by a HbA1c \>9%
• •Impossibility to interrupt short-acting octreotide for 24 h before and 24 h after the administration of 177Lu-DOTA-EB-TATE; impossibility to have an interval of ≥4 weeks between octreotide and 177Lu-DOTA-EB-TATE
• •The use of somatostatin and its analogues within 4 months of a planned 177Lu-DOTA-EB-TATE treatment
• •Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• •Prior external beam radiation therapy involving \>25% of the bone marrow
• •Unmanageable urinary incontinence rendering the administration of 177Lu-DOTA-EB-TATE unsafe
• •Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and with no evidence of recurrence