Her2 is expressed in ~25% of breast cancers and correlates with highly aggressive disease. Her2-targeted therapies are highly efficacious against Her2-positive cancer, yet no clinical imaging agents can assess Her2 status in vivo. EvoRx Technologies has developed a method to discover cyclic peptides that have antibody-like affinities and selectivities, high stability in serum, and rapid systemic clearance. In our Phase I contract, we showed that EVO- 004 has rapid, high levels of tumor uptake with minimal background in mouse models, developed an efficient, automated radiochemical synthesis, and obtained preliminary PET/CT images in mice showing specific tumor uptake as well as rapid clearance and low liver uptake. In Phase II, we aim to complete pre-clinical experiments, enabling first-in-human PET/CT imaging studies with EVO-004. We will use mouse model imaging studies of primary and metastatic cancer models to establish the sensitivity and limit of detection for Her2-positive disease, optimize EVO-004 radiochemical synthesis for clinical production, perform GMP validation studies, and establish dosimetry in rodent and primate models to determine tracer toxicity and establish the maximum safe dose for patient trials. Lastly, we will obtain an IND to deploy our PET tracer in patients with Her2-positive inflammatory breast cancer to demonstrate safety and concordance with biopsy-proven Her2-positive disease.
Public Health Relevance Statement: Public Health Relevance: Molecular imaging can improve clinical choices for breast cancer treatment. We propose to develop more accurate and non-invasive imaging molecules to identify patients who would benefit from targeted cancer therapies. This technology will reduce the need for invasive biopsies and unnecessary surgeries and provide physicians with a powerful tool to personalize breast cancer treatment.
NIH Spending Category: Bioengineering; Breast Cancer; Cancer; Diagnostic Radiology; Precision Medicine
Project Terms: Affinity; Antibodies; Benchmarking; Binding; bioimaging; Biopsy; Blood Circulation; bone; Breast Cancer Patient; Breast Cancer Treatment; Cancer Center; Cancer Model; Chemicals; Chemistry; Clinical; Clinical Trials; Collaborations; Communities; Contracts; Contrast Media; Cyclic Peptides; Data; Detection; Development; Diagnosis; Disease; Dissection; Disseminated Malignant Neoplasm; Dose; dosimetry; Drug Kinetics; Drug usage; fluorodeoxyglucose positron emission tomography; Goals; Health Care Costs; Human; Image; imaging agent; Imaging Techniques; improved; in vivo; inflammatory breast cancer; Injection of therapeutic agent; instrument; interest; Label; Lead; Lesion; Liver; malignant breast neoplasm; Malignant Neoplasms; Metabolism; Methods; milligram; Modeling; Molecular; molecular imaging; Monitor; Morbidity - disease rate; mouse model; Mus; Neoplasm Metastasis; Noise; non-invasive imaging; novel; optical imaging; Organ; outcome forecast; Pathology; Patients; Penetration; Peptide Hydrolases; Peptides; PET/CT scan; Pharmaceutical Preparations; Phase; phase I trial; Physicians; Positron-Emission Tomography; pre-clinical; precision medicine; prevent; Primates; Process; Production; Protocols documentation; public health relevance; Quality Control; Radiation; radiochemical; Radiochemistry; Radiolabeled; radiotracer; receptor; Recurrence; Recurrent disease; Reproducibility; Research Infrastructure; research study; Resistance; response; Risk; Rodent; Safety; scaffold; Serum; Signal Transduction; Small Business Innovation Research Grant; Specificity; Sterility; synthetic peptide; targeted cancer therapy; targeted treatment; Technology; Testing; Therapeutic Studies; Time; Tissues; tool; Toxic effect; Tracer; Trastuzumab; Treatment Efficacy; tumor; Unnecessary Surgery; uptake; validation studies; Variant; Work
