99mTc-DARPinG3-based HER2 Expression Molecular Imaging in HER2-positive Breast Cancer During Chemo+Targeted Therapy

SPECT Imaging of Human Epidermal Growth Factor Receptor 2 (HER2) Using 99mTc-DARPinG3 in HER2-positive Breast Cancer Patients in Dynamic of Chemo+Targeted Therapy

An open-label, single center study with 99mTc-DARPinG3 SPECT and biopsies of primary tumour in HER2-positive Breast Cancer in dynamic of chemo+targeted therapy, where the primary endpoint of the study is to find out the correlation between the HER2 expression measured by 99mTc-DARPin G3 SPECT and standard histopathology from primary tumor in dynamic of chemo+targeted therapy.

none Methodology: Open-label, exploratory, single center study. The subjects will receive a single injection of the labelled tracer.

Inclusion Criteria:

1. Subject is > 18 years of age;

2. Diagnosis of primary breast cancer with tumour size ≥ 20 mm and with possible lymph node metastases;

3. Availability of results from HER2 status previously determined on material from the primary tumor: HER2-positive, defined as a DAKO HercepTest™ score of 3+ or FISH positive;

4. In neoadjuvant all patients should receive standard chemo-targeted therapy according to the DCH+P (docetaxel + carboplatin+ trastuzumab+ pertuzumab) scheme;

5. Injection of 99mTc-DARPinG3 at the dosage 3000 µg before and after 2 and 4 courses of chemo+targeted therapy in each HER2-positive breast cancer patient;

6. Biopsies should be performed in all patients HER2-positive breast cancer patients before and after 2 and 4 courses of chemo+targeted therapy with evaluation of HER2 expression;

7. Hematological, liver and renal function test results within the following limits:

   • White blood cell count: > 2.0 x 109/L
   • Hemoglobin: > 80 g/L
   • Platelets: > 50.0 x 109/L
   • ALT, ALP, AST: =< 5.0 times Upper Limit of Normal
   • Bilirubin =< 2.0 times Upper Limit of Normal
   • Serum creatinine: Within Normal Limits

8. A negative pregnancy test for all patients of childbearing potential. Sexually active women of childbearing potential participating in the study must use a medically acceptable form of contraception for at least 30 days after study termination;

9. Subject is capable to undergo the diagnostic investigations to be performed in the study;

10. Informed consent

Exclusion Criteria:

1. Second, non-breast malignancy
2. Active current autoimmune disease or history of autoimmune disease
3. Active infection or history of severe infection within the previous 3 months (if clinically relevant at screening) 4. Known HIV positive or chronically active hepatitis B or C
4. Administration of other investigational medicinal product within 30 days of screening
5. Ongoing toxicity > grade 2 from previous standard or investigational therapies, according to US National Cancer Institute's