Study to Evaluate the Safety and Activity (Including Distribution) of 177Lu-3BP-227 in Subjects With Solid Tumours Expressing Neurotensin Receptor Type 1.
Study to Evaluate the Safety and Activity (Including Distribution) of 177Lu-3BP-227 in Subjects With Solid Tumours Expressing Neurotensin Receptor Type 1.
This study is being done because new treatment for patients with metastatic or locally
 advanced cancers expressing Neurotensin receptor 1 (NTSR1) is being studied. This study will
 be the first administration of a radioactive drug called 177Lu-3BP-227 to patients under
 controlled conditions of a clinical study. The purpose of this study is to evaluate how safe
 this investigational drug is as well to verify how well it is tolerated by patients after
 several intravenous administrations. In addition, we will evaluate the effect of the study
 drug on tumoral lesions and how it distributes throughout the body and at which rate it is
 removed from the body. Since 177Lu-3BP-227 is a radio-labelled drug, it will also be measured
 how the emitted radiation is distributed throughout the body (dosimetry).

 The study consists of a phase I with a dose escalation part (and potential expansion cohorts)
 and a phase II either in selected or over multiple indications in a basket approach. For the
 dose escalation part, it is anticipated that approximately 30 subjects will be included, in
 up to six escalation steps. In case of the implementation of phase I expansion cohorts, up to
 45 additional subjects will be enrolled. For the phase II, approximately 125 subjects (55
 Pancreatic ductal adenocarcinoma and 70 Colorectal cancer subjects) are planned to be
 enrolled for Basket trial or Optimal Simon's Two Stage design. If additional cohorts of
 subjects with Gastric cancer (GC) or Squamous-cell carcinoma of head and neck (SCCHN) in the
 phase II are to be studied, approximately 100 additional subjects will be enrolled.
Inclusion Criteria :

 -  Signed informed consent form prior to all study procedures

 -  Aged 18 years or older.

 -  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.

 -  Subjects have (a) pancreatic ductal adenocarcinoma (PDAC), or (b) colorectal cancer
 (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)

 -  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.

 -  Measurable disease (based on RECIST version1.1).

 -  Documentation of progressive disease in the 6 months prior to study start (treatment).

 -  Eastern Cooperative Oncology Group performance status of 0 or 1 (unless if disability
 is related to surgery in ES and Agreed with the Sponsor).

 -  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.

 -  Estimated life expectancy >3 months.

 -  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.

 -  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 :

 -  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.

 -  Brain metastases.

 -  Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject
 at high risk of renal toxicity during the study.

 -  Only non-measurable metastatic bone lesions

 -  Existing or planned colostomy during study participation.

 -  Any history of inflammatory bowel disease.

 -  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.

 -  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.

 -  Previously received external beam irradiation to a field that includes more than 30%
 of the bone marrow or kidney.

 -  Any unresolved NCI-CTCAE Grade 2 or higher toxicity (except alopecia) from previous
 antitumor treatment and/or medical/surgical procedures/interventions.

 -  Known allergy to IMP or its excipients administered in this study, including imaging
 contrast media.

 -  Positive pregnancy test (female subjects).

 -  Likely to be uncompliant or uncooperative during the study, in the judgment of the
 investigator.

 -  Unable to understand the nature, scope, and possible consequences of the study, in the
 judgment of the investigator.

 -  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.