Study to Evaluate the Safety and Activity (Including Distribution) of 177Lu-3BP-227 in Subjects With Solid Tumours Expressing Neurotensin Receptor Type 1.

Inclusion

• Brain metastases.
• Measurable disease (based on RECIST version1.1).
• Documentation of progressive disease in the 6 months prior to study start (treatment).
• Tumour showing: (a) by uptake of 177Lu-3BP-227 (screening formulation) in known primary or metastatic sites as judged by the investigator to be greater than background; or (b) uptake of 111In 3BP 227 in known primary or metastatic sites (for subjects who participated in Study D FR 01087 002) as judged by the investigator to be greater than background.
• Sponsor employees or investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• Adequate organ function as evidenced by: (a) Leukocytes ≥3000/μL (b) Absolute neutrophil count ≥1500/µL (c) Platelets ≥75,000/µL (d) Hb \>9 g/dL or \>10 g/dL (if history of cardiac disease) (e) Total serum bilirubin ≤2 times upper normal institutional limits (ULN) (f) Aspartate aminotransferase/alanine aminotransferase (ALT) ≤2.5×ULN (or ≤5×ULN, if subject has liver metastases) (g) Estimated glomerular filtration rate (eGFR) ≥55 mL/min.
• Any uncontrolled significant medical, psychiatric or surgical condition or laboratory finding, that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results.
• Eastern Cooperative Oncology Group performance status of 0 or 1 (unless if disability is related to surgery in ES and Agreed with the Sponsor).
• Inclusion Criteria :
• Must be willing and able to comply with study restrictions and to remain at the clinic for the required time during the study period and willing to return to the clinic for the follow-up evaluation, as specified in the protocol.Exclusion Criteria :
• Any history of inflammatory bowel disease.
• Prior treatment received (a) Any antitumor treatment since last documented disease progression (b) Any chemotherapy within 3 weeks or nitrosourea within 6 weeks prior to first treatment investigational medicinal product (IMP) administration (c) Any curative radiotherapy within 4 weeks, or palliative radiotherapy within 7 days prior to first treatment IMP administration (d) Any monoclonal antibodies within 4 weeks or tyrosine kinases inhibitors within 2 weeks prior to the first treatment IMP administration, (e) Any other IMP within 2 weeks prior to first treatment IMP administration, if the previous compound is a mechanism-based molecularly targeted agent whose half-life (t1/2) is not well-characterized.
• Any unresolved NCI-CTCAE Grade 2 or higher toxicity (except alopecia) from previous antitumor treatment and/or medical/surgical procedures/interventions.
• Likely to be uncompliant or uncooperative during the study, in the judgment of the investigator.
• Known allergy to IMP or its excipients administered in this study, including imaging contrast media.
• Only non-measurable metastatic bone lesions
• Unable to understand the nature, scope, and possible consequences of the study, in the judgment of the investigator.
• Positive pregnancy test (female subjects).
• Histologically or cytologically confirmed unresectable locally advanced or metastatic disease and has received prior lines of standard-of-care chemotherapy/treatment and has no further suitable treatment options and documented decision by a multidisciplinary oncology board including a specialist of the concerned pathology.
• Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study.
• Estimated life expectancy \>3 months.
• Subjects have (a) pancreatic ductal adenocarcinoma (PDAC), or (b) colorectal adenocarcinoma (CRC), or (c) gastric adenocarcinoma (GC), or (d) gastrointestinal stromal tumours (GIST), or (e) squamous-cell carcinoma of head and neck (SCCHN), or (f) Ewing Sarcoma (ES)
• Clinically significant abnormalities on electrocardiogram (ECG) at screening including corrected QT interval (Fridericia's formula) \>450 msec for males or 470 msec for females at screening.
• Existing or planned colostomy during study participation.
• Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.
• Female subjects must not be pregnant or lactating at study entry and during the course of the study and must not become pregnant for at least 6 months following the last study treatment. Women of childbearing potential must agree to use a highly effective method of contraception
• For male subjects, must not father children during the study and for at least 6 months after the last study treatment and in addition must agree to use a condom for this period to protect his partner from contamination with the IMP. For males with partners who are of child bearing potential, effective contraception is a combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods), but these are not considered to be highly effective. A man is considered to be infertile if he has had bilateral orchidectomy or successful vasectomy. Effective contraception includes a female partner of childbearing potential if she is using highly efficacious contraception, but the male subject must agree to use a condom to protect his partner as described above.

Exclusion

Exclusion criteria not yet provided.