The study should evaluate distribution of 99mTc-ZHER2:41071 Affibody molecule in patients with primary HER2-positive and HER2-negative breast cancer

The primary objectives are:

1. To assess distribution of 99mTc-ZHER2:41071 in normal tissues and in tumors over time;
2. To evaluate dosimetry of 99mTc-ZHER2:41071;
3. To obtain initial information concerning safety and tolerability of 99mTc-ZHER2:41071 after single intravenous injection:

The secondary objectives are:

1. To compare the tumor imaging data with the data concerning HER2 expression obtained by immunohistochemistry (IHC) and/or fluorescent in situ hybridization (FISH) analysis of biopsy samples.

Overall goal of the project: To determine HER2 expression level in primary breast cancer and possibly in axillary lymph node metastases before neoadjuvant targeted (trastuzumab or trastuzumab+pertuzumab) therapy.

Phase I. Distribution of 99mTc-ZHER2:41071 in patients with primary breast cancer.

The study should evaluate distribution of 99mTc-ZHER2:41071 in patients with primary HER2-positive and HER2-negative breast cancer.

The primary objectives are:

1. To assess distribution of 99mTc-ZHER2:41071 in normal tissues and in tumors over time;
2. To evaluate dosimetry of 99mTc-ZHER2:41071;
3. To obtain initial information concerning safety and tolerability of 99mTc-ZHER2:41071 after single intravenous injection:

The secondary objectives are:

1. To compare the tumour imaging data with the concerning HER2 expression obtained by immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH) analysis of biopsy samples:

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 possible lymph node metastases

3. Availability of results from HER2 status previously determined on material from the primary tumor, either

   1. HER2-positive, defined as a DAKO HercepTest™ score of 3+ or FISH positive or
   2. HER2-negative, defined as a DAKO HercepTest™ score of 0 or 1+; or else if 2+ then FISH negative

4. Volumetrically quantifiable tumour lesions on CT or MRI, with at least one lesion > 2.0 cm in greatest diameter outside of the liver and kidneys

5. 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

6. 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

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

8. 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
5. Administration of other investigational medicinal product within 30 days of screening
6. Ongoing toxicity > grade 2 from previous standard or investigational therapies, according to US National Cancer Institute's

Women with primary breast cancer