eoRay - Phase I/IIa trial of [177Lu]-NeoB in patients with advanced solid tumors and with [68Ga]-NeoB lesion uptake.

Phase 1

• Conditions: Solid tumors known to overexpress GRPR and with [68Ga]-NeoB lesion uptake; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004727-37-NL
• Lead Sponsor: Advanced Accelerator Applications International SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-30
• Last Update Posted: 8 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

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 including HER-2 low as assessed on the primary diagnosis.
b. Cohort B: Prostate cancer
c. Cohort C: GIST
d. Cohort D: patients affected by any advanced/metastatic solid tumor type known 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
e. Cohort E: (only performed in the US and UK)
3. At least one measurable lesion per RECIST 1.1, RANO (applicable for GBM only) criteria detected on the low-dose CT or on the 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

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, C and E)
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 (NYHA 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 (IMP2).
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 treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to [177Lu]-NeoB treatment; completely resected basal cell and squamous cell sk

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified