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 metastatic or locally advanced disease and
no compelling treatment option as per standard-of-care 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
- Tumour tissue expressing NTSR1 as determined by uptake of 177Lu-3BP-227 (screening
formulation) in tumour lesions judged by the investigator to more avid than in the
non-tumoral surrounding tissue based on whole body scan (planar scintigraphy); single
photon emission computed tomography (SPECT)/ computed tomography (CT) can be performed
as per investigator's judgement.
- 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. Because CT scanning is part of the long-term follow-up (every
12 ±2 weeks), female subjects should not become pregnant until the end of study
- 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 antitumour treatment since last documentation of
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-characterised.
- 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
antitumour treatment and/or medical/surgical procedures/interventions.
- Known allergy to IMP or its excipients administered in this study, including imaging
- Positive pregnancy test (female subjects).
- Likely to be uncompliant or uncooperative during the study, in the judgment of the
- 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.