Lung cancer is one of the most common types of cancer in the United States and, by far, the leading cause of cancer deaths. According to the National Cancer Institute (NCI), more than 234,000 Americans were diagnosed with lung cancer in 2018. An estimated 154,000 Americans died from lung cancer in 2018, more than three times more than colorectal cancer, the next most deadly cancer, according to the NCI. Lung cancer accounts for 25 percent of all cancer deaths in the United States.

There are two main types of lung cancer: Non-small cell lung cancer accounts for 80-90 percent of all lung cancers. Non-small cell lung cancer has several subtypes, but most are adenocarcinomas of the lung. Lung adenocarcinomas account for 30 percent of all non-small cell lung cancers and 40 percent of all lung cancers, according to the American Cancer Society.  The second main type is small cell lung cancer. Ten to 20 percent of lung cancers are small cell lung cancers. This type of lung cancer is most commonly associated with tobacco smoking.

What makes lung cancer so difficult to treat and deadly is the difficulty of diagnosing the disease at beginning stages. Given the challenges of using biomarkers for early diagnosis there is much enthusiasm for the potential of using non-invasive liquid biopsy tests to provide that early warning system.

Inivata, based in the UK has been an early pioneer in developing liquid biopsy tests for cancer including the lung. It had developed one of the few advanced stage lung cancer liquid biopsy tests on the markets and is working to pave the way for more effective testing at earlier stages. A non-invasive liquid biopsy offers a revolution in how cancer is detected, monitored and treated, providing the potential for frequent tumor profiling and a more personalized approach to cancer care.

As part of the WuXi Communications program to highlight innovative solutions to develop novel drugs and tests that can make a difference in patients’ lives, WuXi spoke with Inivata CEO Clive Morris about his company’s new liquid biopsy technology and how it might develop to give doctors and patients tools to discover lung cancer at a, more treatable stage.

Morris joined the leadership team in May 2016 and became CEO in July 2018.  Morris worked for over a decade in various key roles at AstraZeneca, where he oversaw R&D and led the major transformation of AstraZeneca’s UK strategic R&D sites and global HQ. He has extensive experience across all phases of drug development including seven marketed or close-to-market oncology products. Most recently Morris founded and led Health Innovation Manchester, to develop an innovation ecosystem involving the decentralization of £6bn per annum of health and social care services. Morris is accredited as a Pharmaceutical Medicine specialist by the UK Royal College of Physicians, has an Executive MBA and Honorary Professorship of Translational Medicine at the University of Manchester, and trained as a physician at the University of Manchester.

WuXi: What is your opinion about the challenges in lung cancer early diagnosis? Are there any specific biomarkers?

Clive Morris: One of the key challenges in treating lung cancer is the late presentation of symptoms. The notable symptoms of early-stage disease are similar to other conditions that are more common in the population making early suspicion more difficult. Diagnosis of early-stage lung cancer using biomarkers is challenging given the requirements on sensitivity and specificity and the fact that in early-stage disease the levels of blood based markers are very low. There is lots of excitement for detection of cancer including lung cancer using liquid biopsies, but more work is required before it is ready for the mainstream.

WuXi: What are the hot targets in the field of testing for lung cancer?

Clive Morris: As well as research into early detection, we have products and more advanced development programs addressing other unmet clinical needs. The first liquid biopsy tests are now approved for guiding therapy in patients with advanced lung cancer, with Inivata being one of the two companies reimbursed for clinical use in the US market. There is increasing data supporting the potential for early detection of response to therapy and relapse, as well as resistance mechanism detection. What is particularly exciting is the use of liquid biopsy tests to detect the presence of residual disease post-surgery in early stage cancer, to guide the use of adjuvant therapies. Such tests also potentially allow the monitoring of patients for relapse following surgery. To be successful in this setting, tests will need to have exquisitely high sensitivity and specificity and Inivata is working on such an approach.

WuXi:  What types of testing modalities show the most potential? Are there any with the potential to treat early stage disease?

Clive Morris: It is important to match the right technology and the right test for each application. To help guide treatment of advanced cancers by approved targeted therapies, it is important to have high sensitivity for actionable variants, and less important to cover a long list of exploratory or research targets. This has been the rationale behind the development of Inivata’s InVisionFirst-Lung test, which has been demonstrated to have best-in-class sensitivity for actionable variants. For early detection, it is important that a test has a high specificity to avoid a low predictive value. To detect minimal residual disease with high sensitivity and specificity, an ideal test would have high sensitivity for each marker and would cover a large number of variants or markers that are relevant for each patient. This consideration is guiding the design of our development program in this area.

WuXi: How is your test different from existing lung cancer tests? Is it a new approach? What have been the results of your research so far?

Clive Morris: Our currently approved InVisionFirst-Lung liquid biopsy test helps to identify the therapeutics that should be considered in patients with advanced lung cancer by detecting the most clinically relevant genomic alterations that drive lung cancer and are associated with approved therapeutics. This has historically been undertaken by the testing of tumor tissue removed from the patient via an invasive tissue biopsy, but this procedure is expensive, has frequent complications and a high failure rate. It can also take a number of weeks to schedule and undertake the biopsy and have the tumor material tested for genomic alterations. Using a liquid biopsy like InVisionFirst-Lung can lead to more genomic alterations being detected to prevent the complications and cost of invasive tissue biopsies and can help enable patients to receive the appropriate therapy more rapidly.

WuXi: How did you choose to focus on lung cancer? It has been a very difficult disease to treat.

Clive Morris: This high unmet need is exactly why we have chosen to focus on lung cancer. Great strides have been made in the development of targeted therapeutics for genomically defined subsets of lung cancer, but these cannot help the patients unless they can be quickly and reliably tested for the alterations. This is where our test can help. Our product pipeline includes products that address additional areas of unmet need including better monitoring of response to therapeutics, detection of residual disease following surgery of curative intent to better guide adjuvant therapy provision, and minimally invasive monitoring for evaluation of disease free/recurrence status in patients being followed up after surgery for early stage cancer.

WuXi: How can you maximize the value and benefit of your test for as many patients as possible globally?

Clive Morris: Inivata has a broad portfolio of products in the pipeline. In order to reach as many patients as possible globally, we plan to work with world-leading partners across the world, in addition to commercializing our products ourselves. We recently announced that we have appointed a distributor in the Middle East and Africa, IPS Genomix, and we are actively seeking strong partners to help us in our mission to transform the lives of cancer patients.

WuXi: What major challenges have you faced in trying to bring a new test for lung cancer to patients?

Clive Morris: The first step was to create a technology that is able to detect the very few tumor-derived DNA fragments in a blood sample collected from a cancer patient. To achieve this, we developed the InVision platform, which we’ve shown to be the most sensitive gene panel for high-sensitivity liquid biopsies. There are also challenges associated with changing the standard of care with a new paradigm and it takes time to shift perceptions in a field where there can also be confusion with a number of seemingly competing technologies, some of which may not reach the market.

WuXi: Have you benefitted from FDA initiatives, such as breakthrough and fast track designations?  If so, how?

Clive Morris: We have engaged with FDA, and indeed we have a breakthrough device status for the early detection of therapeutic response in patients with advanced lung cancer. This program is still relatively recent, so its full impact will be felt in the years to come, but it is intended to help speed the development and regulatory path of critical technologies that help to address areas of significant unmet need.

WuXi: What are the top three major impediments in our delivery of “better” medicines “faster” and “better” to patients?

Clive Morris: Although major progress has been made in the development of therapies for genomically defined subsets of lung cancer, the patients cannot be treated without fast and reliable testing. Better monitoring of the response to therapies is also required to ensure that patients continue to receive the most appropriate treatment and, alongside this, we need to be able to detect residual disease following surgery through minimally invasive techniques that can ensure the optimal patient experience. Our current test and further product pipeline are able to address each of these challenges to enable quicker, better treatments in a more effective manner to patients.

WuXi: For lung cancer what would be the one thing that has the most potential to lead a paradigm shift “from treatment to cure.”

Clive Morris: Lung cancer is a complex multi-factorial disease so one solution is unlikely to work for all. The reality will be that better early diagnosis to help find patients with disease that can be cured by surgery is important. Also important is to better guide adjuvant therapy to those who actually need it, and not to over-treat those already cured. More effective, less invasive and more sensitive methods for the detection of relapse and sensitive tests to guide advanced cancer therapies are all important steps in improving the management of patients with lung cancer.