174TiP - A pivotal clinical trial of a functional ex vivo organ culture assay for cancer precision medicine

Background

Precision cancer therapy has the potential to revolutionize treatment outcome. While genomic analysis has become central to cancer personalized medicine, recent studies have shown that it can improves survival in only a minority of the patients. Additionally, genomic mutations may suggest several treatment protocols without elucidating which approach will yield the best clinical response. To advance cancer precision guidance, we have developed cResponse®, a combined genomic-functional drug sensitivity platform to determine individualized patient treatment regimens. Fresh patient cancer samples are taken by biopsy or resection and sectioned into 250uM slices which demonstrate similar architecture and tissue proliferation to those found in vivo. An initial clinical study showed that cResponse® can preserve human cancer tissue in 3D culture together with its microenvironment, including endothelial and immune cells, at a high viability (>90%) with continued cell division for more than 7 days. On a cohort of 34 patients treated with neoadjuvant therapy or systemic therapy for metastatic disease, the assay was able to predict patient response to drug treatment with a sensitivity of 96% and a specificity of 77.7%.

Trial Design

To further validate the capacity of cResponse® to predict patient response to cancer therapy, a follow up pivotal clinical study was established in the UK with the goal of recruiting a total of 170 patients to provide a large statistical validation of the previous results. Patient cancer samples were received and evaluated with the intended to treat therapy, and their cResponse® score was matched to their RECIST data to establish sensitivity, specificity, PPV and NPV. Here we report on the outcome of the first cohort of patients recruited to the pivotal trial, confirming the ability of the platform to accurately preserve a patients cancer tissue with intact tumor microenvironment for 5 days and describing the predictive results correlated to patient response.

Editorial acknowledgement

Clinical trial identification

NCT04599608; Last update posted 2020-10-22.

Legal entity responsible for the study

Curesponse.

Funding

Curesponse.

Disclosure

S. Hanks, N. Costelloe, S. Salpeter, V. Bar, A. Zundelevich: Financial Interests, Personal, Other, Employee: Curesponse.G. Neev, R. Straussman: Financial Interests, Personal, Leadership Role: Curesponse. All other authors have declared no conflicts of interest.