Periodic Reporting for period 2 - CytoPro (A breakthrough cancer diagnostic instrument to save 3000 years of human lives annually and up)
Berichtszeitraum: 2020-05-01 bis 2021-06-30
The lifetime risk of developing cancer is increasing, with an incidence of approximately 1 in 2 people developing cancer in their lifetime in the western world. Targeted cancer therapies are often considered the most effective, developed to block tumour growth with molecular precision and based on the genetic profile of the patient’s cancer when they first present for treatment. In the case of metastatic colorectal cancer (mCRC), the second biggest cancer killer, 40% of patients are resistant to the most common mCRC targeted therapy (cetuximab) at baseline, and with the remaining 60% of patients, resistance can emerge at any stage during treatment but it will remain undetected until shown on CT scans. There is no diagnostic tool available today that can monitor for these genetic changes on a regular basis (e.g. every 4 weeks). As a result, health services spend over €1.5bn p.a. on expensive targeted treatments that for a significant part are ineffective as the patient’s resistance goes undetected for months, while at the same time the patient gets more ill and also suffers unnecessarily from serious side effects of the treatment.
Effective use of targeted therapies relies on getting up-to-date genetic information obtained from tumour material. This is often feasible in mCRC at the beginning of treatment by performing a biopsy on the primary tumour after its surgical removal. Testing for the same genetic information during treatment could be possible via biopsy of metastatic tumours but this is not always an option with mCRC due to tumour location. It is also painful, can lead to medical complications and due to risk cannot be performed frequently enough to monitor cancer progression. These limitations have driven a search for an alternative, non-invasive biopsy technique for cancer patients so that cancer mutations can be monitored.
Novel non-invasive approaches, often known as liquid biopsies, have been developed to use blood samples to monitor and predict cancer progression. Liquid biopsies offer clear benefits to oncologists and patients, as they are suited to regular monitoring of metastasis. CytoTrack has developed such a method by monitoring the level of ‘circulating tumour cells’ (CTCs) in the blood. CTCs are an aggressive type of cancer cell that “seed” from tumours and travel to distant organs via the blood to form metastases (the cause of death in 90% of cancer cases). Because it is these CTCs which are the most prolific cells, they are believed to represent the most up-to-date information on cancer mutation status and have great potential for guiding therapy.
The CytoTrack patented CT11™ platform can quickly and accurately identify and isolate CTCs so that these cells can be genetically characterized. The CT11™ makes it possible to cost-effectively determine whether cancer cells have developed a resistance to the targeted therapy and allow an oncologist to change towards a more effective therapy in time.
The overall objectives of this project were to validate CytoTrack’s CT11™ instrument in a multi-centre clinical trial with 350 mCRC patients and take the device from the Research Use Only (RUO) environment where it already exists into clinical practice. The project was intended to demonstrate that liquid biopsies can become mainstream practice for monitoring cancer progression and that the CT11™ is a reliable instrument for performing these liquid biopsies.
Effective use of targeted therapies relies on getting up-to-date genetic information obtained from tumour material. This is often feasible in mCRC at the beginning of treatment by performing a biopsy on the primary tumour after its surgical removal. Testing for the same genetic information during treatment could be possible via biopsy of metastatic tumours but this is not always an option with mCRC due to tumour location. It is also painful, can lead to medical complications and due to risk cannot be performed frequently enough to monitor cancer progression. These limitations have driven a search for an alternative, non-invasive biopsy technique for cancer patients so that cancer mutations can be monitored.
Novel non-invasive approaches, often known as liquid biopsies, have been developed to use blood samples to monitor and predict cancer progression. Liquid biopsies offer clear benefits to oncologists and patients, as they are suited to regular monitoring of metastasis. CytoTrack has developed such a method by monitoring the level of ‘circulating tumour cells’ (CTCs) in the blood. CTCs are an aggressive type of cancer cell that “seed” from tumours and travel to distant organs via the blood to form metastases (the cause of death in 90% of cancer cases). Because it is these CTCs which are the most prolific cells, they are believed to represent the most up-to-date information on cancer mutation status and have great potential for guiding therapy.
The CytoTrack patented CT11™ platform can quickly and accurately identify and isolate CTCs so that these cells can be genetically characterized. The CT11™ makes it possible to cost-effectively determine whether cancer cells have developed a resistance to the targeted therapy and allow an oncologist to change towards a more effective therapy in time.
The overall objectives of this project were to validate CytoTrack’s CT11™ instrument in a multi-centre clinical trial with 350 mCRC patients and take the device from the Research Use Only (RUO) environment where it already exists into clinical practice. The project was intended to demonstrate that liquid biopsies can become mainstream practice for monitoring cancer progression and that the CT11™ is a reliable instrument for performing these liquid biopsies.
Manufacturing: production and assembly of our 3 instruments in parallel was completed and fine tuning was performed. Machines were dispatched to Erasmus Medical Centre (EMC) in Rotterdam and MSCNRIO in Warsaw.
Development of Assay: we worked with Erasmus to establish the sequencing panel and the assay method for CTC characterisation but the development of the assay was not completed.
Clinical Protocol: the study protocol was finalised with our three collaborating centres and submitted to the Ethics Committees in three countries (NL, PL and DK).
European and US patents: the US patent for our device was granted in April 2020. The European patent status is "intention to grant" ready for it to be ratified in each state.
Development of Assay: we worked with Erasmus to establish the sequencing panel and the assay method for CTC characterisation but the development of the assay was not completed.
Clinical Protocol: the study protocol was finalised with our three collaborating centres and submitted to the Ethics Committees in three countries (NL, PL and DK).
European and US patents: the US patent for our device was granted in April 2020. The European patent status is "intention to grant" ready for it to be ratified in each state.
The global burden of colorectal cancer is anticipated to increase by 60% by 2030 and yet ongoing testing for predictive biomarkers is still not in routine use for CRC patients. We know that clinicians anticipate that biomarkers will become routinely used to guide personalised medicine and that there is an expectation that there will also be a low-cost and high performance tool to optimise cancer drug selection for patients in the clinic, but as yet, this is not in use.
Our devices will now be on loan to research labs in Poland and Denmark and independent research on CTC detection will continue with these labs. We have made provisions to allow for researchers to continue to use our device to demonstrate mutational shifts during treatment. In due course we hope the results of this independent research will offer sufficient insight to tailor treatment for patients, providing the often quoted “right treatment for the right patient at the right time”. Furthermore, we expect that the examination of CTCs will indicate disease progression before this progression can be seen on the patient's usual 8 weekly CT scan. Despite the project terminating prematurely due to shortage of funding, we believe that progress will be made in CTC/cancer research with the CT11 instruments.
Our devices will now be on loan to research labs in Poland and Denmark and independent research on CTC detection will continue with these labs. We have made provisions to allow for researchers to continue to use our device to demonstrate mutational shifts during treatment. In due course we hope the results of this independent research will offer sufficient insight to tailor treatment for patients, providing the often quoted “right treatment for the right patient at the right time”. Furthermore, we expect that the examination of CTCs will indicate disease progression before this progression can be seen on the patient's usual 8 weekly CT scan. Despite the project terminating prematurely due to shortage of funding, we believe that progress will be made in CTC/cancer research with the CT11 instruments.