AVB-620 is an intravenously administered protease-activatable fluorescent peptide that utilizes ratiometric detection to intraoperatively visualize cancer. The initial indication is intraoperative identification of primary tumor extent and metastatic lymph nodes in breast cancer patients. AVB-620 displayed outstanding preclinical data with accuracy >95% in in vivo breast cancer models and 92% in ex vivo analysis of human breast cancer tissue. AVB-620 has completed a Phase 1b clinical trial assessing safety, pharmacokinetics and fluorescence properties using tissue image analysis. A Phase 2 clinical trial for AVB-620 in breast cancer was initiated in June 2017.

AVB-620 is administered to patients prior to surgery and fluorescence imaging is performed with a camera system. The diagnostic readout is displayed on a monitor with normal surgical field for the surgeon. The diagnostic fluorescence signal may enable the surgeon to identify critical cancer margins and stage lymph nodes. This capability may enable surgeons to make real-time decisions to improve medical treatment and lead to significant cost savings by reducing surgical time and reducing the number of re-operations.

Breast Cancer: Unmet Need

Surgical margins

For surgery for the removal of the primary tumor in the breast, achieving a “negative” margin is a key element for decreasing local recurrence. Current standard practice for intraoperative margin analysis is primarily limited to the surgeon’s ability to discriminate cancerous tissue by sight and feel.  The need to return for a second surgery to re-excise the margins is typically reported as ranging between 20-40% with some centers reporting re-excision rates as high as 70%. Consequences of a return to the operating room include an increase in infection rates, a delay in starting needed chemotherapy or radiation therapy, worse cosmesis from removing extra tissue, and a proportion of women choosing mastectomy for their second operation.  There is also a 2x higher rate of local recurrence in patients with positive margins.  Importantly, current techniques are only focused on tissue removed during surgery.  Products like AVB-620 may allow the surgeon to examine the surgical cavity for any cancerous tissue that would be left behind.

Sentinel Lymph Node Biopsy:

Sentinel lymph node biopsy (SLNB) has been widely adopted as a less invasive surgical alternative to axillary lymph node dissection (ALND) for staging early breast cancer.   When SLNB indicates axillary disease is not present, patients may be spared ALND surgery.  This strategy reduces the risk of complications and long-term morbidity, such as lymphedema. In addition to resection of the primary tumor, all invasive breast cancers require assessment of lymph nodes for tumor invasion.  Assessment of the axillary nodes includes SLNB during lumpectomy or at the time of mastectomy.    In addition to helping determine the need for ALND, nodal status provides critical staging information necessary for the proper selection of adjuvant therapy.  Negative findings after SLNB allow a patient to avoid the potential significant morbidity associated with full axillary dissection.  This strategy reduces the risk of immediate complications and long-term arm morbidity.  A recent analysis estimates that 79% of SLNB-positive procedures incurred a second operation for ALND at a later date.  The cost-effectiveness of SLNB would be even more favorable if it were possible to identify and manage SLNB-positive cases at the time of initial operation, avoiding re-operation and a second hospital admittance.  Products like AVB-620 may allow the surgeon to provide a full assessment during the initial procedure, thus reducing the need for a second surgical procedure.