An International Multicentre, Open-Label First in Human Phase I/II study to evaluate the safety, tolerability, biodistribution and antitumour activity of 177Lu-3BP-227 for the treatment of subjects with solid tumours expressing neurotensin receptor 1
- Conditions
- metastatic or locally advanced cancers expressing Neurotensin Receptor 1 (NTSR1).10027476
- Registration Number
- NL-OMON50308
- Lead Sponsor
- Ipsen Pharma SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
Phase I
Eligible subjects meet all the following inclusion criteria:
(1) Signed informed consent form prior to all study procedures.
(2) Aged 18 years or older.
(3) Histologically or cytologically confirmed unresectable or locally advanced
or metastatic disease and has received prior lines of standard-of-care
chemotherapy/treatment and has no further suitable treatment option and a
documented decision by a multidisciplinary oncology board including a
specialist of the concerned pathology.
(4) Subjects have:
(a) PDAC or,
(b) CRC or,
(c) GC or,
(d) GIST or
(e) SCCHN or
(f) ES.
(5) Tumour showing:
(a) 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.
(6) Measurable disease (based on RECIST version 1.1).
(7) Criterion 7 is removed by protocol amendment.
(8) Documentation of progressive disease in the 6 months prior to study start
(treatment).
(9) Eastern Cooperative Oncology Group performance status of 0 or 1 (unless
disability is related to surgery in ES and agreed by the sponsor).
(10) Adequate organ function as evidenced by:
(a) Leukocytes *3000/*L
(b) Absolute neutrophil count *1500/*L
(c) Platelets *75,000/*L
(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) eGFR *55 mL/min.
(11) Estimated life expectancy of 3 months.
(12) 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 (see note below).
(13) 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 (see note below), but the male subject must agree to
use a condom to protect his partner as described above.
(14) 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 followup evaluation, as specified in the protocol.
Phase II
The inclusion criteria for phase II will be revised based on the scenario
adopted and indication(s) selected for investigation in phase II. This will be
documented as part of a protocol amendment.
Phase I/II
Eligible subjects must not have any of the following conditions:
(1) Prior treatment received
(a) Any antitumour treatment since last documented disease progression
(b) Any chemotherapy within 3 weeks or nitrosourea within 6 weeks prior to
first treatment 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 t1/2 is not
well-characterised.
(2) Brain metastases.
(3) Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting
the subject at high risk of renal toxicity during the study.
(4) Only non measurable metastatic bone lesions
(5) Existing or planned colostomy during study participation.
(6) Any history of inflammatory bowel disease.
(7) 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.
(8) Clinically significant abnormalities on ECG at screening including
corrected QT interval (Fridericia's formula) >450 msec for males or 470 msec
for females at screening.
(9) Previously received external beam irradiation to a field that includes more
than 30% of the bone marrow or kidney.
(10) Criterion 10 is removed by protocol amendment.
(11) Any unresolved NCI-CTCAE Grade 2 or higher toxicity (except alopecia) from
previous antitumour treatment and/or medical/surgical procedures/interventions
(12) Known allergy to IMP or its excipients administered in this study,
including imaging contrast media
(13) Positive pregnancy test (female subjects).
(14) Likely to be uncompliant or uncooperative during the study, in the
judgment of the investigator.
(15) Unable to understand the nature, scope and possible consequences of the
study, in the judgment of the investigator.
(16) 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.
Eligibility criteria for phase II will be reviewed as soon as phase I results
are available.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method