CuRrEnT: Capecitabine in RCB2/3 with a wearable induced Electric field device in Triple Negative Breast Cancer

PROJECT SUMMARY/ABSTRACT Triple-negative breast cancer (TNBC) is challenging to treat clinically as it is highly invasive, has a high risk of relapse, metastasizes, and has a very poor prognosis. Patients experience disease progression even with improved chemotherapy, immunotherapy, and surgery. About 40% of stage I-III TNBC patients receiving standard of care (SOC) rapidly relapse with distant metastases, peaking 3 years after diagnosis. In analysis of the Keynote-522 clinical trial data, patients with higher residual cancer burden (RCB) experienced worse event free survival rates. The SOC for a most patients with relapse or difficult-to-treat conditions is cytotoxic chemotherapy, which only has response rates of 10%-15% in pre-treated patients, and short progression-free survival. To date, only pharmacological therapies has been approved for treating TNBC. Therefore, novel effective therapeutic monotherapies must be developed that also complement standard treatments for TNBC. To meet this urgent clinical need, EMBioSys has developed an innovative therapeutic device that is a novel wearable, washable garment (camisole/tank-top) to deliver induced electric field (iEF) therapy, a non-ionizing electromagnetic (EM) radiation treatment that poses no risks and targets cancer cells with metastatic potential. With EM fields of intermediate frequency (< 500 kHz) and low intensity (µV/cm–mV/cm), we have already shown in preclinical TNBC mouse models that iEF treatment significantly decreases distant metastases to the lungs, primary tumor burden, infiltration of pro-metastatic immune cells, and increased infiltration of anti-tumor activated cytotoxic T cells in the primary tumor microenvironment (TME). This novel iEF therapy elicits potent beneficial and selective response against TNBC by modifying endogenous electric fields (and voltages) that exist both at the tissue and cellular levels, by introducing externally applied voltages and electric fields that hinder tumor growth and metastasis to the lungs (on-going phase I SBIR award 1R43CA287836-01 animal study). This contact-free (i.e. requiring no electrodes or contact required with skin), non-invasive treatment has been shown to be safe with no adverse events in animals. In this Direct-to-Phase II application we will develop and manufacture to good manufacturing practice (GMP) the first ever wearable, washable, electrode-free, garment (camisole/tank-top) to non-invasively administer induced electric field (iEF) therapy in human patients. The objectives are to confirm that iEF therapy poses no safety risk to patients and to establish its anti-tumor and anti- metastasis activity in a first-in-human trial when used with adjuvant SOC treatment in high-risk patients. Successful completion of this work will add a non-toxic, non-pharmacological therapy to medical oncologists’ arsenal of existing pharmacological therapies which patients can easily tolerate, increase time to recurrence or altogether eliminate recurrence, and potentiate SOC. Collectively, this work has the potential for saving the lives of patients with metastatic TNBC who are not responsive to current standard of care.