A Phase I/IIa open-label, multi-center study to evaluate the safety, tolerability, whole-body distribution, radiation dosimetry and anti-tumor activity of [177Lu]-NeoB administered in patients with advanced solid tumors known to overexpress gastrin-releasing peptide receptor (GRPR)
- Conditions
- Advanced solid tumors known to overexpress GRPRAdvanced solid tumorsgastrin-releasing peptide receptor10027655
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
1. Signed informed consent must be obtained prior to participation in the
study.,
2. Adult patients (age >= 18 years old) with any of the following advanced or
metastatic solid tumors:
• For Phase I: breast cancer, lung cancer, prostate cancer, GIST, GBM
• For Phase IIa:
a. Cohort A: Breast cancer with histology as follows: HR- positive with ER >
10% of nuclei stain, HER-2 negative and HER-2 low based on current practice and
medical history.
b. Cohort B: Prostate cancer
c. Cohort C: GIST
d. Cohort D: patients affected by any advanced/metastatic solid tumor type
suspected to overexpress GRPR including recurrent GBM, and with moderate
impaired renal function defined as creatinine clearance (calculated using the
Cockcroft-Gault formula, or measured) >= 30mL/min and < 60mL/min.,
3. At least one measurable lesion per RECIST 1.1 RANO (applicable for GBM only)
criteria detected on the low-dose CT/MRI (for GBM MRI only) acquired together
with the [68Ga]-NeoB PET. The same identified measurable lesion shows
[68Ga]-NeoB uptake on PET/CT or PET/MRI. If the only matching lesion is located
in the bone, the patient will still be eligible.,
4. Patients for whom no standard therapy is available, tolerated or appropriate
in both Phase I and Phase IIa. Specifically in the Phase IIa breast cancer
cohort, patients need to have completed at least one prior treatment of
endocrine therapy (including CDk4/6i) and at least one prior chemotherapy
(unless contraindicated) in the metastatic setting. Patients with prior
treatment with trastuzumab deruxtecan, alpelisib or elascestrant are also
eligible. In case of confirmed presence of deleterious or suspected deleterious
germline BRCA1 or BRCA2 mutation, the patient must also have already received a
PARP inhibitor based therapy.
5. Patient Eastern Cooperative Oncology Group (ECOG) performance status:
For phase I: <= 2
For phase IIa: <= 1
1. Patients who have not had resolution, except where otherwise stated in the
inclusion/ exclusion criteria, of all clinically significant toxic effects of
prior systemic cancer therapy, surgery, or radiotherapy to Grade <=1 (except for
alopecia).
2. Creatinine clearance (calculated using Cockcroft-Gault formula, or measured):
a. < 60 mL/min or serum creatinine >1.5 x ULN* for Phase I and Phase IIa
(Cohort A, B and C)
b. <30 mL/min and >= 60 mL/min for Phase IIa (Cohort D)
3. Platelet count of < 75 x 10^9/L*.
4. Absolute neutrophil count (ANC) < 1.0 x 10^9/L*.
5. Hemoglobin < 9 g/dL*.
6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x
upper limit of normal (ULN) if no demonstrable liver metastases or > 5 x ULN in
the presence of liver metastases*.
7. Total bilirubin > 1.5 x ULN, except for patients with documented Gilbert*s
syndrome who are eligible if total bilirubin <= 3 x ULN*.
8. Serum amylase and/or lipase > 1.5 x ULN*.
9. Known or expected hypersensitivity to [177Lu]-NeoB, [68Ga]-NeoB or any of
their excipients.
10. Impaired cardiac function or clinically significant cardiac disease,
including any of the following:
* Clinically significant and/or uncontrolled heart disease such as congestive
heart failure requiring treatment (New York Heart Association (NHYA) grade >=
2), uncontrolled arterial hypertension or clinically significant arrhythmia
* LVEF < 50% as determined by echocardiogram (ECHO)*
* QTcF >470 msec for females and QTcF >450 msec for males on screening
electrocardiogram (ECG) or congenital long QT syndrome
* Acute myocardial infarction or unstable angina pectoris < 3 months prior to
[177LU]-NeoB (IMP1) administration.
11. Patients with diabetes mellitus not stable under current treatment as
judged by the investigator, or with hyperglycemia >= CTCAE version 5.0 grade 2*.
12. Patients with history of or ongoing acute or chronic pancreatitis.
13. Concurrent bladder outflow obstruction or unmanageable urinary incontinence.
14. Administration of a radiopharmaceutical with therapeutic intent within a
period corresponding to 10 half-lives of the radionuclide used prior to
injection of [68Ga]-NeoB.
15. Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone
marrow.
16. [223Ra]-therapy within the context of diffuse bone or bone marrow
involvement (i.e. superscan defined as bone scintigraphy in which there is
excessive skeletal radioisotope uptake [>20 bone lesions] in relation to soft
tissues along with absent or faint activity in the genitourinary tract due to
diffuse bone/bone marrow metastases).
18. Patients who have received prior systemic anti-cancer treatment within the
following time frames:
* Cyclical chemotherapy within a period that is shorter than the cycle length
used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to
starting [177Lu]-NeoB treatment
* Biologic therapy (e.g. antibodies), continuous or intermittent small molecule
therapeutics, or any other investigational agents within a period which is <= 5
T1/2 or <= 14 days (whichever is shorter) prior to starting [177Lu]-NeoB
treatment.
19. History of somatic or psychiatric disease/condition that may interfere with
the objectives and assessments of the study.
20. Malignant disease, other than that being tr
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy:<br /><br>Tumor assessment per RECIST v1.1, RANO (applicable for GBM only)<br /><br><br /><br>Key safety assessments:<br /><br>Incidence and severity of Adverse Events (AEs) and Serious Adverse Events<br /><br>(SAEs), including changes in laboratory values, vital signs, and<br /><br>Electrocardiograms (ECGs) for [177Lu]-NeoB; Incidence and severity of Adverse<br /><br>Events (AEs) and Serious Adverse Events (SAEs) for [68Ga]-NeoB. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Other:<br /><br>PK for all patients as well as distribution and radiation dosimetry for at<br /><br>least the first 3 patients treated at each dose level of [177Lu]-NeoB in phase<br /><br>I, the first 6 patients treated in cohorts A, B, and C, and all patients<br /><br>treated in cohort D in Phase IIa. </p><br>