Lung cancer is one of the most common malignancies and a leading cause of cancer death. The majority of patients (~85%) are diagnosed with non-small-cell lung cancer (NSCLC). Therapies are based on chemotherapeutic agents, immunotherapy and targeted therapies to inhibit somatic mutations in tumor promoting genes such as KRAS, BRAF, EGFR, MET, ALK, ROS. The efficacy of these treatments is limited due to therapeutic resistance leading to disease progression. In order to evaluate the response to a new treatment, patients are followed-up by imaging including CT, PET-CT and MRI. These radiology scans are usually performed 6-8 weeks after treatment initiation. To optimize treatment and to avoid ineffective treatments, non-invasive and rapid predictive tools are urgently required. The potential clinical utility of circulating cell-free DNA (cfDNA) mainly in serum and plasma is an area of active research. Increased levels of cfDNA have been observed in patients with cancer. A recent retrospective analysis of data from the ALEX clinical study suggested that plasma cfDNA concentration may have prognostic value in advanced NSCLC. Several studies in NSCLC patients showed that transient elevation in circulating tumor DNA (ctDNA) levels immediately following targeted therapy initiation correlated with tumor response to therapy. We developed an at-home collection kit for cfDNA quantification in urine. This kit is a non-invasive tool to be used for predicting the response to a new treatment (Figure 1) as well as monitoring tumor burden along treatment.  The use of this kit is expected to provide early information on treatment efficacy, to decrease the amount of required radiology scans and to allow earlier detection of drug resistance and disease progression, thereby enabling clinicians to optimize personalized therapy.
The technology was developed in collaboration with: Prof. Amir Onn, Sheba medical center. 

UNMET NEED
• There is a need for an early indication of treatment response in NSCLC and many other cancers. The current standard-of-care imaging are done 6-8 weeks after treatment initiation.
• There is a need for a monitoring biomarker for NSCLC patients along treatment. 

OUR SOLUTION
At-home urine collection kit to quantify cfDNA levels:
• Early information on treatment efficacy (8 days instead of 6-8 weeks) 
• Earlier detection of drug resistance and disease progression
• Non-invasive
• Inexpensive
• At-home sample collection 
• Urine cfDNA stabilization

APPLICATIONS
• A non-invasive biomarker to monitor treatment efficacy
• A non-invasive biomarker to monitor disease progression
• A companion diagnostic test for targeted therapy 

STATUS
• We are analyzing NSCLC patients in 2nd + line and expanding to other cancers 
• Currently there are no commercially available tests in this short duration after treatment initiation 

INTELLECTUAL PROPERTY
A priority patent application was filed in the US on 28 December 2022: METHODS AND KITS FOR DETERMINING PERSONALIZED TREATMENT REGIMEN.

REFERENCES
1. Trans-Renal Cell-Free Tumor DNA for Urine-Based Liquid Biopsy of Cancer. Sarah M Dermody, Chandan Bhambhani , Paul L Swiecicki, J Chad Brenner, Muneesh Tewari. Front. Genet. 2022
2. Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non-small Cell Lung Cancer in the Global Phase III ALEX Trial. Rafal Dziadziuszko, Solange Peters, Tony Mok, D Ross Camidge, Shirish M Gadgeel, Sai-Hong Ignatius Ou, Krzysztof Konopa, Johannes Noé , Malgorzata Nowicka, Walter Bordogna, Peter N Morcos, Vlatka Smoljanovic, Alice T Shaw. Clinical Cancer Research 2022