Molecular Imaging of HER2 Expression in Breast Cancer Using 99mTc-ZHER2

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:

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

The secondary objectives are:

• 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

• Subject is > 18 years of age
• Diagnosis of primary breast cancer with possible lymph node metastases
• Availability of results from HER2 status previously determined on material from the primary tumor, either

• HER2-positive, defined as a DAKO HercepTest™ score of 3+ or FISH positive or
• HER2-negative, defined as a DAKO HercepTest™ score of 0 or 1+; or else if 2+ then FISH negative
• 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
• 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
• 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
• Subject is capable to undergo the diagnostic investigations to be performed in the study
• Informed consent

Exclusion criteria

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