Biocept Believes ctDNA, CTCs Both Hold Promise in Future of Liquid Biopsy

This year is poised to be a breakthrough year in the adoption of liquid biopsy technology. Biocept (San Diego) is in position to be at the forefront of this emerging market with a growing menu of tests for both circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) on the company’s proprietary OncoCEE and CEE-Selector platforms. To date, the company has released commercial tests for breast, gastric and non-small cell lung cancer and has a robust pipeline of additional tests focused on solid tumor biomarkers in colorectal, prostate, and melanoma. DTET recently spoke to Biocept CEO Michael Nall regarding recent developments at the company and the broader outlook for adoption of the liquid biopsy technology.
How would you characterize the current state of clinical adoption of liquid biopsy technology? We see liquid biopsy being adopted in three phases. The first phase, where we are today, is using liquid biopsy to fulfill a true unmet medical need—when a biopsy is just not adequate or even possible to obtain. We see this in lung cancer patients most often, but it also could be in metastatic cancer for all types of solid tumors. The most common sites for metastasis are bone, brain, lung, and liver, which are all areas where it would be difficult to obtain a tissue biopsy for molecular profiling. Oncologists really have to have this molecular information to make the appropriate clinical decisions. That is the first phase of liquid biopsy adoption. The second phase seems to be coming along really quickly. There are some real tailwinds this year, for monitoring. Once these patients have been put on these therapies because of a certain molecular alteration, there is a need to monitor them. Previously molecular alterations were only assessed using tissue biopsies, but you can’t turn someone into a pincushion and keep performing biopsies on them all of the time. That is just not practical. But, with blood we can monitor these patients. One of the first areas we see this occurring clinically is for lung cancer patients on tyrosine kinase inhibitors (TKIs), like Tarceva. We can monitor their EGFR status through a blood sample. That’s very meaningful for oncologists and we see this occurring. Additionally, you can look for resistance by monitoring certain markers, like T790M. The reason I said there are some tailwinds is that there are some promising drugs in clinical trials and clinicians will need to know that T790M resistance status to move patients to those new therapies. We see a third phase in the future for identifying recurrence and for a screening assay down the road done with a liquid biopsy. Within fi e years, I anticipate a lot of movement in this area of screening. We are already starting to see research using CTCs as well as ctDNA and you can find cancer earlier than tumors show up in scans. There is a lot of potential with screening here, but it is going to take investment and proof-of-concept supported by positive clinical trials to get us where we need to go with the technology.
There seems to be some debate over the value of CTCs versus ctDNA. Biocept has tests for both. Where do you see the value of each of these methods? There is a lot of debate when you go to industry conferences, with some people saying you’ve got to be in CTCs because you need the context of the cell to make sure you are in a cancer cell. But, you also have other people saying with plasma you are more likely to get a result. We think all parts of the cell are important. There is a future in all parts of liquid biopsy. Using CTCs we have launched assays for breast cancer and lung cancer. But, with ctDNA we can detect mutations like EGFR in a very quick, straightforward, and sensitive way. To me there are true limitations if you go only to plasma. For instance, isn’t protein of interest in these cells? That’s not something you are likely to do with a plasma-based assay. We are currently collaborating with a couple of partners on microRNA and RNA detection and that is something you are unlikely to get out of plasma. Those are examples of where CTCs are very valuable. Why would you say I don’t need one or the other? It’s all part of the cell and it is all interesting.
Do you see liquid biopsy opportunities outside of oncology? We are really focused on oncology today. I think there are many applications in cardiology and, maybe even someday, in Alzheimer’s. But today Biocept is focused on cancer and there are plenty of diagnostic targets in the space.
In which sub-areas of oncology do you see the most interest in liquid biopsies? A lot of what we are doing is in lung. Lung cancer biopsies are exceptionally difficult to obtain. Fine needle aspirate and core-needle biopsy yield very small amounts of tissue. It is not uncommon that there is not enough tissue for molecular testing. There is a true, true need to help these patients, so we are focusing a lot of our efforts there as well as in treatment monitoring. Because of these new agents there is a real need to identify that resistance earlier in treatment. Lung cancer is the low-hanging fruit. In the metastatic, recurrent population for breast and gastric cancer, you run into the same problems. You can’t do some tests on bone and you certainly aren’t going to do a biopsy with a brain mass. So, in that population there is a real need for this test.
Stakeholders still struggle with a universal standard for establishing proof of clinical utility. How is Biocept addressing generation of evidence? We know that with reimbursement there is a high hurdle. We do have reimbursement for most of our tests we do because we use established CPT codes for these mutations. We do get paid today, unlike a company running unique algorithmic assays that must appeal denials with miscellaneous codes. We still need to continue to demonstrate clinical utility, though, to drive adoption and receive adequate reimbursement from payers. We have taken a first step to establish clinical validity and clinical utility. The papers that have been published by our academic collaborators thus far show a very high correlation between our tests and with tissue, which has been the gold standard. This year we are moving forward with additional studies that take it to the next step—incorporating patient response to therapeutic choice as an endpoint. It will be important to move clinicians and patients away from tissue biopsy and towards blood-based tests. In addition, we need to prove in a journal a concept that is common sense to everyone—the idea that doing a blood test instead of a surgical procedure can save hundreds of millions, if not billions of dollars for the U.S. health care system. Nobody would argue with the assumption, but we need to prove it.
Uncertainty remains regarding future regulation of laboratory-developed tests (LDTs). Do you believe this uncertainty affects adoption? At Biocept we continue to keep an eye on developments and are awaiting final guidance for LDTs. We are engaged with industry consultants and are part of the 21st Century Medicine Coalition. We are trying to develop our strategy as much as possible. I don’t see adoption being affected by this debate at all. It’s mainly an internal debate between regulatory bodies and the laboratory industry. I’m not sure how much clinicians are aware of this debate or that it affects their decision-making. That said, this discussion is certainly important to our company. At Biocept we are well suited for the possibility of future regulation. We manufacture the microfluidic device we use for CTC capture and we control that process, which we think will be an advantage if we do need to secure U.S. Food and Drug Administration (FDA) clearance or approval. In addition, once we capture the CTCs we use kits that have been approved by the FDA. We source companion diagnostic kits from Abbott so we are in a way doing an approved assay. We are just doing it on tumor cells out of blood, not tumor cells out of tissue.
In the coming years how do you see cancer testing evolving? We are going to see a further evolution toward genomics. I anticipate a movement toward broader tumor profiling with diagnosis. At the start, you will need to qualify a patient with a big genomic profile comparing germline and somatic mutations. From there, there is this huge opportunity in treatment monitoring. More specifically, with liquid biopsy, it makes sense to monitor patients with more targeted assays. In the future, possibly in the five- to 10-year timeframe, there will be a way to make truly personalized assays, based on that tumor’s unique genomic signature. These assays will help clinicians monitor their patients for treatment response, resistance, and cancer recurrence. When it comes to screening, the medical community must do a better job. Looking at lung cancers or other cancers with such a high mortality rate underscores this need for improved screening. Part of the problem is that patients are being diagnosed at such a late stage. Our current mode of screening for lung cancer is problematic. Screening through a blood test for the molecular basis of disease offers an improved opportunity. It’s early to say how broad cancer screening will be. In the nearer term we can do a better job screening at-risk populations, say smokers, with a targeted assay. However, in the long term, there are nearly limitless opportunities in the space and the many different ways screening could evolve.