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, by NCI Staff

SARS-CoV-2 virus particles (orange) isolated from a patient at the NIAID Integrated Research Facility in Fort Detrick, Maryland. Credit: National Institutes of Health

In her spare time last year, Neelam Giri, M.D., joined an effort to test fellow NIH employees for SARS-CoV-2, the coronavirus that causes COVID-19. She administered the test to many employees with symptoms of COVID-19 in their cars outside the NIH Clinical Center in all kinds of weather.

For Dr. Giri, a staff clinician in NCI’s Division of Cancer Epidemiology and Genetics (DCEG), the testing was volunteer work. And in December, she became one of the first frontline workers at the Clinical Center to receive the Moderna COVID-19 vaccine.

“I’m honored to be part of this campaign to end the pandemic,” Dr. Giri said before receiving the vaccine at an event to kick off COVID-19 vaccinations among NIH employees. Her volunteer job illustrates one of the many ways that cancer researchers have been working against COVID-19.

Since the pandemic began, cancer researchers have also been contributing their expertise and resources to scientific investigations of the coronavirus. Their findings have been broad in scope, ranging from insights into how the virus enters cells to the identification of potential therapies.

For example, cancer researchers reported recently that antibodies to SARS-CoV-2 may protect people from being reinfected by the virus. The research was part of NCI’s ongoing response to the pandemic, which also includes a study of patients with cancer and COVID-19 and studies of genomic factors that influence the severity of the disease.

As the pandemic continues, the results of these and other studies could inform the prevention and treatment of COVID-19 among individuals with and without cancer, according to cancer researchers who have investigated SARS-CoV-2.

“Many cancer researchers have been able to pivot portions of their research—either in the laboratory or in the clinic—to try to better understand COVID-19 and find ways to treat the disease,” said James Gulley, M.D., Ph.D., head of the immunotherapy section of NCI’s Center for Cancer Research (CCR).

Cancer researchers are well suited to investigate COVID-19 “because we are used to dealing with complex biological problems,” Dr. Gulley continued. And some of the tools used to study how the immune system interacts with tumors can be modified to study SARS-CoV-2, he added.

Testing Biomarkers for the Severity of COVID-19

Last spring, for example, several cancer researchers in New York City shifted their focus from studying immunotherapy—treatments that help the immune system to detect and kill cancer cells—to investigating the body’s response to the coronavirus.

Sacha Gnjatic, Ph.D., of the Icahn School of Medicine at Mount Sinai and his colleagues identified proteins called cytokines that could be indicators, or biomarkers, of the severity of COVID-19 and the response to treatment. Increased blood levels of two cytokines—IL-6 and TNF-a—were associated with poor survival and severe forms of COVID-19 in a large group of hospitalized patients.

The results suggested that these cytokines could potentially guide decisions about the type of care that people with COVID-19 should receive, Dr. Gnjatic said. “Such biomarkers could be evaluated in future clinical trials,” he added.

About 10% of the patients with COVID-19 in the study also had cancer. “We are still analyzing the data to see whether there are certain factors that make these patients more likely to develop severe COVID-19 than other patients,” said Dr. Gnjatic.

He brought to the project his experience leading an NCI-sponsored initiative to develop biomarkers that doctors could use to identify patients with cancer who are likely to respond to immunotherapy drugs.

“We are interested in the interplay between tumors and the immune system,” said Dr. Gnjatic. “When COVID-19 hit, we were primed to use our research methods to investigate the pathology of the disease.”

Starting in March, Dr. Gnjatic co-led a team of researchers at Mount Sinai Hospital that created a COVID-19 research biobank. In just two months, the biobank collected blood samples from 500 patients hospitalized with COVID-19. Since then, the biobank has added samples from nearly 300 hospitalized patients, and all of these patients have been followed over time.

“We now have at least 6 months of follow-up data,” Dr. Gnjatic said. “The biobank will allow us to analyze many more biomarkers, predict patient outcomes, assess the impact of treatment, and hopefully contribute to better clinical care of patients with COVID-19.”

Investigating COVID-19 in People with Cancer

Researchers have reported that people with cancer may be at an increased risk of developing more serious forms of COVID-19.

“The prior therapies that patients with cancer have had may make them more likely to get sick from COVID-19,” said Nirali Shah, M.D., of CCR, who co-led a clinical trial testing the drug tocilizumab (Actemra) in patients with cancer and COVID-19. Cancer and certain treatments for cancer, she noted, can weaken the immune system.

Patients with cancer also tend to be older and may have risk factors linked to aggressive forms of COVID-19, noted Ziad Bakouny, M.D., of the Dana-Farber Cancer Institute, who coauthored a recent overview of cancer and COVID-19. These risk factors include certain underlying health conditions, such as diabetes and a heart condition.

“In general, patients with cancer have more severe COVID-19 symptoms at diagnosis and, unfortunately, they also have worse outcomes than patients who don’t have cancer,” Dr. Bakouny said.

More research, he continued, is needed to understand “how the biology of cancer and COVID-19 may interact in individuals with both diseases.”

Some answers may come from the NCI COVID-19 in Cancer Patients Study (NCCAPS). In this natural history study, researchers are collecting data, blood samples, and images from people with cancer and COVID-19. Participants will provide blood samples at multiple time points over a 2-year period.

“We expect that the samples and data we are collecting will help researchers to better understand many aspects of how COVID-19 is affecting patients with cancer,” said Larissa Korde, M.D., of NCI’s Cancer Therapy Evaluation Program and a leader of the NCCAPS study.

The researchers have been enrolling children and adults at some 700 sites across the country, including sites that are part of the NCI Community Oncology Research Program (NCORP). NCORP reaches patients in underserved areas, many of which have been disproportionately affected by the pandemic.

The results will complement findings from the COVID-19 and Cancer ConsortiumExit Disclaimer, a research study involving 125 hospitals across the country that is collecting data about people diagnosed with COVID-19 and cancer, noted Dr. Korde.

Revealing Clues to Coronavirus Infections and Treatment Possibilities

Some cancer researchers, including DCEG’s Ludmila Prokunina-Olsson, Ph.D., have focused on the underlying biology of coronavirus infections.

Last fall, her team described a previously unknown form of ACE2, the receptor protein used by the coronavirus to bind to and infect cells. The newly identified molecule—now called deltaACE2 (dACE2)—is shorter than the other form of ACE2 and does not appear to bind to SARS-CoV-2, which means that it is unlikely to be a gateway for viruses to enter human cells, said Dr. Prokunina-Olsson.

The researchers also found that certain cells, including some tumor cells, produce dACE2 when exposed to interferons. The body makes interferons in response to viral infections; interferons are also synthetically produced as drugs to treat cancer, infections, and other diseases. In clinical trials, researchers have been testing interferons as possible treatments for COVID-19.

In their study, Dr. Prokunina-Olsson and her colleagues found that the full-length ACE2 protein did not appear to be produced by cells in response to exposure to interferons or viruses, as some previous studies had suggested.

Taken together, the new findings suggest that exposure to viruses or interferons used for treatment may lead to the expression of dACE2 rather than the full-length form of the ACE2 receptor—and would therefore not increase the risk of cells being infected by SARS-CoV-2.

Two other groups of researchers recently confirmed the existence of dACE2 in human cells. “We are conducting additional experiments to understand why and when dACE2 is produced by normal and tumor cells—and whether differences in the expression of ACE2 and dACE2 could be important for infection,” said Dr. Prokunina-Olsson.

Profiling T-Cell Responses to the Coronavirus

Cancer researchers have also been investigating the body’s response to SARS-CoV-2, including the role that immune cells called T cells may play in fighting the infection.

“T cells can identify cells that have been infected by the virus and kill those cells,” said Dr. Gulley. “We think that studying T cells will be important for understanding the immune system’s response to SARS-CoV-2 as well as the immune response to vaccines against the virus.”

In cancer immunotherapy research, investigators routinely monitor how T cells are turned on, or activated, in response to certain proteins (antigens) on tumor cells. “We can bring this experience to the fight against COVID-19,” said Dr. Gulley.

Some of Dr. Gulley’s colleagues in CCR have done just that. A team led by Jeffrey Schlom, Ph.D., and Renee Donahue, Ph.D., has adapted tests used to profile T-cell responses to tumor antigens for studies of the coronavirus.

“As COVID-19 emerged, we modified the tests so that we could specifically measure T-cell responses against certain parts of the coronavirus, such as the spike protein on the surface of the virus and the nuclear protein,” said Dr. Donahue, of the Laboratory of Tumor Immunology and Biology.

The new technology “offers a very sophisticated way of looking at T cells and determining how active they are against certain viral proteins,” said Dr. Gulley.

The tests could be used to study COVID-19 vaccines in patients with cancer who are receiving immunotherapy, noted Dr. Donahue. “We need to learn whether COVID-19 vaccines can generate effective immune responses in patients being treated for cancer,” she added.

Understanding Inflammatory “Storms”

In some patients with severe COVID-19, the immune system mounts an overly aggressive response to the virus. When this happens, the body may produce large numbers of cytokines. By stimulating the immune system, these proteins can damage vital organs, such as the lungs and the heart, leading to death. This hyperinflammatory state is sometimes called a cytokine storm.

Uncontrolled immune responses involving cytokines can also occur in patients with cancer who receive immunotherapy drugs known as CAR T-cell therapies. In these patients, the phenomenon—called cytokine release syndrome—occurs when large amounts of cytokines are released into the blood all at once.

Such responses can be life-threatening, so patients receiving immunotherapy are routinely monitored for evidence of aggressive immune responses and treated as needed.

Although some of the same cytokines may be involved in responses to CAR T-cell therapy and to the coronavirus, the underlying biology of these responses is different, Dr. Shah explained.

“Fundamentally, what is happening with COVID-19 is that an infection leads to an inflammatory response,” said Dr. Shah.

“There may be direct or indirect injury to tissue as a result of COVID-19, and this could lead to very different immune responses,” she continued. “Also, for a host of reasons, some patients may have more of an inflammatory response than others.”

Understanding why people can have such different responses to infection with the coronavirus is the focus of ongoing investigations. For example, the NIH-led COVIDcode study is examining how genetic variants may contribute to the severity of COVID-19.

Testing Potential Treatments for COVID-19

Cancer researchers have also played a role in identifying and evaluating potential treatments for overactive immune responses associated with COVID-19. Several cancer drugs—or drugs being studied as cancer treatments—have been evaluated for this purpose.

“The results of these studies have been mixed, and more research is needed to determine which treatments may be effective,” said Dr. Bakouny, who noted that certain steroids have been shown in clinical trials to treat overactive immune responses associated with COVID-19.

One of the first cancer drugs to be evaluated for COVID-19 was acalabrutinib (Calquence). This treatment blocks the activity of a protein called Bruton’s tyrosine kinase (BTK), which plays an important role in the normal immune system.

Last March, a team led by Wyndham Wilson, M.D., and Louis Staudt, M.D., Ph.D., in CCR launched a small study to test acalabrutinib in 19 patients hospitalized with severe COVID-19.

The researchers had conducted the studies that led to acalabrutinib’s approval for certain types of lymphoma and leukemia. Some of this research had suggested that BTK inhibitors could impair the body’s immune response.

“We took the knowledge we had about the drug from our cancer studies and tried to apply that to the treatment of patients with COVID-19 who had the most dramatic immune responses,” said NCI’s Mark Roschewski, M.D., who helped conduct the study.

In the study, some of the 19 patients seemed to benefit from the drug. But in a subsequent randomized clinical trial, the drug did not improve the number of patients who were alive and free of respiratory failure, according to the maker of acalabrutinib, AstraZeneca.

Nonetheless, the research on BTK inhibitors that began during the pandemic will continue through a study called RESPOND, which is led by the National Institute of Allergy and Infectious Diseases.

“What we learn may help us understand how these inhibitors could potentially be useful for the treatment of other common inflammatory and autoimmune conditions that afflict the general population,” said the study’s lead investigator, Michail Lionakis, M.D., Sc.D., who also collaborated on the NCI-led acalabrutinib research.

An Unprecedented Pace of Scientific Discovery

Researchers have been studying coronaviruses for decades, Dr. Gulley noted, so investigators “already have a head start on identifying important questions to explore.”

He added, “The more research tools we can bring to this fight—and the more different angles we can come at this virus—the better our chances of gaining insights that will help us to more effectively treat the virus and limit its spread.”

Dr. Prokunina-Olsson said that the pace of scientific discoveries related to COVID-19 has been “unprecedented.” She undertook her study of ACE2 in response to research that had been posted online for the scientific community early in the pandemic.

The practice of sharing scientific results almost in real time fuels new studies and raises additional research questions, Dr. Prokunina-Olsson stressed.

“This process has allowed the research community to conduct follow-up studies and to refine the messages of previous publications,” she said. “What could normally take several years happened in a matter of months.”

WILL COVID-19 BOOST CLINICAL TRIALS AWARENESS?

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From: www.instituteforpatientaccess.org
May 18, 2020

This piece from the Institute for Patient Access gives excellent insight into the massive effects, both positive and negative, the COVID-19 crisis has had on clinical trials.  Although in many cases, resources have been diverted to focus on finding a treatment and possible vaccine for the virus, it is quite possible that an increased awareness of the importance and necessity of clinical trials has been realized across the country and the world. 

This year’s Clinical Trials Awareness Week falls squarely in the midst of the COVID-19 pandemic. The week’s theme, “Clinical Trials During a National Public Health Emergency,” explores how the coronavirus demands and, in some cases, also disrupts clinical research. It also prompts an important underlying question: Once the pandemic subsides, will the public retain a greater awareness and appreciation of clinical trials?

Clinical Trials & the Coronavirus

More than 100 potential novel coronavirus vaccines are being developed by research teams around the globe. In the United States, pharmaceutical companies, university researchers and government agencies are working together to find a vaccine. Meanwhile, the FDA recently approved existing drug remdesivir for emergency use in treating people infected with COVID-19.

But finding effective COVID-19 treatments takes time. Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease, has stated that it will take at least a year or more to provide a workable vaccine.

While this effort moves forward, clinical trials investigating potential medications for non-coronavirus related diseases are being pushed to the back burner. Reporting from NPR indicates that 440 clinical trials, involving as many as 200,000 people, have been suspended because of the coronavirus outbreak. One-quarter of the trials put on hold were exploring cancer treatments, with research on strokes, dementia, and other serious conditions stalled as well.

Clinical trials during the pandemic pose a number of challenges. Researchers and sponsors must decide if enough staff are available, and if visiting health care facilities is worth the risk of virus exposure for trial participants. Meanwhile, data obtained from trials will take longer to develop, with radiology suites and other offices closed.

Clinical Trials Awareness After COVID-19

But the COVID-19 pandemic could also have positive long-term implications for clinical trials.

In years past, people often have had little awareness of clinical trials until they or a family member needed to join one. The lack of knowledge makes clinical trials difficult to enroll and conduct, even under normal circumstances. Over one-third of trial sites fail to meet their enrollment goals, with more than one site in 10 unable to enroll even a single patient.

By elevating public awareness of clinical trials, the COVID-19 pandemic could alter that trend.

If the coronavirus outbreak offers any silver lining, perhaps it’s that the country’s experience could stimulate public interest and participation in future trials, ushering in a period of robust research that yields meaningful treatments for patients, families and communities.

Finding a novel coronavirus vaccine will save lives. But it could also mark the beginning of a greater public awareness of the importance of clinical trials.

Will Covid-19 Boost Clinical Trials Awareness?

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From Institute for Patient Access
May 18, 2020

This year’s Clinical Trials Awareness Week falls squarely in the midst of the COVID-19 pandemic.  The week’s theme, “Clinical Trials During a National Public Health Emergency,” explores how the coronavirus demands and, in some cases, also disrupts clinical research.  It also prompts an important underlying question: Once the pandemic subsides, will the public retain a greater awareness and appreciation of clinical trials?

Clinical Trials & the Coronavirus

More than 100 potential novel coronavirus vaccines are being developed by research teams around the globe.  In the United States, pharmaceutical companies, university researchers and government agencies are working together to find a vaccine. Meanwhile, the FDA recently approved existing drug remdesivir for emergency use in treating people infected with COVID-19.

But finding effective COVID-19 treatments takes time. Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease, has stated that it will take at least a year or more to provide a workable vaccine.

While this effort moves forward, clinical trials investigating potential medications for non-coronavirus related diseases are being pushed to the back burner. Reporting from NPR indicates that 440 clinical trials, involving as many as 200,000 people, have been suspended because of the coronavirus outbreak. One-quarter of the trials put on hold were exploring cancer treatments, with research on strokes, dementia, and other serious conditions stalled as well.

Clinical trials during the pandemic pose a number of challenges.  Researchers and sponsors must decide if enough staff are available, and if visiting health care facilities is worth the risk of virus exposure for trial participants.  Meanwhile, data obtained from trials will take longer to develop, with radiology suites and other offices closed.

Clinical Trials Awareness After COVID-19

But the COVID-19 pandemic could also have positive long-term implications for clinical trials.

In years past, people often have had little awareness of clinical trials until they or a family member needed to join one. The lack of knowledge makes clinical trials difficult to enroll and conduct, even under normal circumstances. Over one-third of trial sites fail to meet their enrollment goals, with more than one site in 10 unable to enroll even a single patient.

By elevating public awareness of clinical trials, the COVID-19 pandemic could alter that trend.

If the coronavirus outbreak offers any silver lining, perhaps it’s that the country’s experience could stimulate public interest and participation in future trials, ushering in a period of robust research that yields meaningful treatments for patients, families and communities.

Finding a novel coronavirus vaccine will save lives. But it could also mark the beginning of a greater public awareness of the importance of clinical trials.

The Pandemic of COVID-19 and its Effect on Clinical Trials in the Community

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James Adkins, SCOR co-principal investigator

James N. Atkins, MD Bon Secours Cancer Institute at St. Mary’s & Co-Principal Investigator, SCOR NCORP, Richmond, VA

This story is part of The Cancer Letter’s ongoing coverage of  COVID-19’s impact on oncology. 

This pandemic has affected a lot of people, both physicians and patients, physically as well as emotionally.

There are patients who have become afraid to come into the office to see the staff for fear that they would contract the virus. Our patients seem to have more depression, which may stem from a lack of social interaction.

We have all had our practices turned upside-down, we have gone from face-to-face visits, which we love, to computer-to-computer, or phone-to-phone visits. We have seen physician reimbursement plummet and colleagues stress about their ability to run a private practice.

Physicians have been concerned about their ability to pay the bills as well as their own mortality from this invisible enemy.

We are seeing PTSD in practitioners.

This virus, like cancer, has turned a lot of lives upside-down, and perhaps has shown us what our patients face on a daily basis.

Some patients whom I have seen have been treated on clinical trials in large cities and have been told that they cannot come back to the city for therapy due to the COVID lockdown. They have been referred to our communities to get their clinical trial therapy.

We are treating patients on clinical trials, but they are on trials that we do not have open. This would have been unheard of a few weeks ago. It would be a major protocol deviation, but should it be?  What can we learn—and what should we learn—from this pandemic when it comes to clinical trials and audit time?

Getting patients in to be seen on time (as per protocol) has been more difficult due to patients’ fear about going to the hospital, a doctor’s office or the concerns about social distancing on the way to or in the office.

In the past, we could get tests done when we wanted them—within a day or two. Now, a CT scan will have to be classified as STAT in order to get it done on a certain date.

We would never had ordered it STAT in the past, as it may cost more; but now we have to. With COVID, the x-ray departments have changed their protocols so as to have more time available for COVID patients and to conserve supplies. So our patients who need x-rays are delayed.

Some of our nursing staff may have been furloughed or redeployed due the pandemic as the hospitals are losing money and they are trying to maintain a balance sheet that is already negative.

One of the offices in our NCORP have had their staff furloughed, with just a manager left behind, 6 of 19 offices are trying to do 75% to 90% of their work remotely, and 10 of 19 continue to work in-house.

There has been a significant decline in NCTN accruals to clinical trials over the past month nationally. It also seems that there has been a significant decrease in new cancers over the past month as well. The decrease in cancers is probably due to people being afraid to come to see a doctor—or the procedures to diagnose the cancer is considered elective.

Some of the practitioners, doctors included, are afraid to see patients for fear that they may get the virus from the patients and then get sick or die. We are seeing more patients with virtual visits, and this is good in that it does decrease the exposure of our patients to others. However, this makes documenting for clinical trials more difficult.

Those of us treating patients worry about deviations from protocols and the protocol violations that then occur.

The good thing is that there are people in the clinical trial organizations and the NCI who do understand what’s going on. We believe that the problems of the pandemic will be considered when it is audit time.

We are having problems getting procedures done like colonoscopies for iron deficiency in the older population, and needle biopsies of lung lesions when we need them. We have found that we have to be more insistent on what we want and when we want it, as others may not understand.

I had a patient who needed a lung biopsy after her third cycles of therapy, and radiology was not very happy, because we already had a diagnosis of lung cancer, we had not been clear enough in our request.

We are also having problems getting tests done within the eligibility time window, just getting pulmonary function tests or a Cardiac Echo may take time.

What can we learn from this pandemic? What can we do to make changes that will improve clinical trials in America? Can we have a system where physicians are approved by some organization as being physicians that have demonstrated good practice with clinical trials and those so designated be allowed to work across trials from different sites?

It seems like we have seen a significant drop in accrual to clinical trials over the past year or two, as trials became more precision-based. COVID has just made this worse.

I fear that we are getting down much closer to 1% of adults going on trials not the 3% of the past. Should a patient be able to go 200-400 miles away to get started on a trial and then be allowed to get some or all of their follow-up treatment closer to home if it is agreeable with all the providers?

I think it is worth considering.

The easier we make it for a patient to go on a clinical trial and the easier we make it for their follow-up, the better we will do with accrual and changing the therapy for cancer.

If this is a time for change, then we need to re-evaluate the barriers for patients going on trial.

These may range from a lack of clinical trial training in our training programs, to physician apathy and burnout, ability to open trials due to lack of staff, patient trust, and financial support just to name a few.

We have to decide how important it is and whether we want to try to fix it—or whether the status quo is acceptable.

Copyright (c) 2020 The Cancer Letter Inc.

At NCI, A Robust and Rapid Response to the COVID-19 Pandemic

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, by Norman E. Sharpless, M.D.

The NCI response to COVID-19 clinical trials

NCI is providing expertise and research capabilities to address the COVID-19 pandemic, including efforts related to serology testing, genomics studies, and drug development.
Credit: National Cancer Institute

Late last week, I convened an emergency meeting of two key NCI advisory boards, the Board of Scientific Advisors and the National Cancer Advisory Board.

This meeting was the first entirely virtual joint gathering of these two boards. It was held so that NCI leadership could bring board members up to date on the institute’s response to the COVID-19 pandemic, and also so that NCI could receive advice from the boards on our pandemic response plans. Watch a recording of the full meeting online.

So much about this meeting was extraordinary, not the least of which are the circumstances that required it. Needless to say, we are in the midst of an extremely challenging time, one marked by significant loss of life, an unprecedented economic downturn, and an unimaginable upheaval in daily life.

At NCI, we know that these problems are particularly acute for people with cancer and their families. Some patients are at higher risk of severe illness from COVID-19 because their cancer, or the treatment of that cancer, has left them weakened and more vulnerable to complications. In addition, many types of effective cancer treatments like palliative chemotherapy, surgery, and radiation have been postponed or cancelled to minimize the risk of exposure to the virus, but leaving these patients at higher risk of suffering from their cancer.

I’ve talked with many of my colleagues in cancer centers across the country, and they are deeply concerned. They and their institutions are also taking whatever steps possible to adapt to the situation as best they can, knowing it won’t always be enough to meet their patients’ needs.

At NCI we’re also adapting to the situation, taking measures to help keep the nation’s cancer research enterprise operating to the fullest extent possible. During last week’s meeting, I stressed to the board members that NCI’s number one priority is, and always will be, advancing cancer research and doing what we can to reduce the burden of cancer.

But I also reminded them that NCI, as the world’s largest cancer research organization, has tremendous expertise and unique research capabilities that make our participation in the response to this pandemic a moral obligation.

Indeed, as an organization, NCI has much to offer, including:

  • a long history of virology research, including work that helped lead to the discovery of HIV and the first AIDS treatments, and the development and broad-scale testing of the HPV vaccine
  • a nationwide research infrastructure that includes large academic institutions with top experts, experienced clinicians, and a proven track record of conducting complex clinical studies
  • a huge portfolio of partnerships and collaborative relationships with government and public health institutions and private-sector companies
  • the Frederick National Laboratory for Cancer Research (FNLCR), which houses advanced technologies and research resources that are of direct and immediate relevance to a viral pandemic

The board meeting largely focused on providing an overview of some of the activities specific to the pandemic NCI has embarked upon in the last 4 to 6 weeks. The sheer amount of work that’s been done, and the speed with which it’s been done, is nothing short of amazing.

Redirecting Resources and Expertise at Frederick National Lab

The FNLCR is the only Federally Funded Research and Development Center (FFRDC) dedicated to biomedical research. Located in Frederick, MD, FNLCR is a research powerhouse with top-notch scientists and cutting-edge technologies. As NCI Deputy Director Doug Lowy, M.D., explained during last week’s board meeting, FNLCR is perfectly suited to respond to a crisis like the coronavirus pandemic. And NCI is bringing those resources to bear in response to COVID-19.

Serology Testing: Assessing the Immune Response

Researchers at FNLCR have launched an initiative focused on serology, a word that, unexpectedly, has now entered the popular lexicon. Serology is the process of measuring a person’s immune response to an infection in the form of antibodies in the blood.

The HPV Serology Laboratory at FNLCR has long played a central role in helping to develop and standardize serology tests for antibodies to cancer-causing HPV types. The lab has been temporarily repurposed to work on serology testing for the novel coronavirus, including working with the Food and Drug Administration (FDA) to validate serology tests submitted to the agency by outside scientists and companies.

Staff in the HPV Serology Laboratory also are collaborating closely with colleagues at the National Institute of Allergy and Infectious Diseases (NIAID), the Centers for Disease Control and Prevention, and several academic medical centers, including several in regions of the country hard-hit by the virus, like New York.

Serology testing will be necessary for the country to return to some semblance of normalcy by, among other things, identifying those who have had an infection and have evidence of immunity from COVID-19. Serology testing is also being used to screen blood from those who have had and recovered from COVID-19 for the production of convalescent plasma, a potential treatment for others with serious disease.

Understanding the Genetics of COVID-19 Outcomes

NCI has also launched a series of genomics studies to try to identify genetic alterations that are associated with good and poor outcomes from COVID-19. One study will specifically focus on people with cancer.

That effort is being led by Stephen J. Chanock, M.D., director of NCI’s Division of Cancer Epidemiology and Genetics—in partnership with investigators from NIAID and the National Human Genome Research Institute—and conducted largely through FNLCR. Using samples collected from people infected with the novel coronavirus, their goal is to rapidly identify genetic variants associated with an individual’s outcome to infection.

The hope is not only to better understand the biology of infection with this particular coronavirus, but also to identify potential targets for new treatments and provide insights that can possibly be used for screening purposes.

An important aspect of this effort will be to rapidly and broadly share the data from these studies with the research community.

Identifying Potential New Therapies for COVID-19

FNLCR is also home to NCI’s RAS Initiative, an effort to develop new therapies for cancers driven by mutated forms of RAS genes, particularly KRAS. Such cancers include highly deadly types like pancreatic and lung cancer, and thus efforts to create RAS-targeted therapies have been a high priority for the cancer research community.

FNLCR is now using some of the advances made via the RAS Initiative to try to identify new therapies for COVID-19. Part of that effort includes a resource, known as a screening library, that has been used successfully to identify chemical compounds that can block the activity of the mutated KRAS proteins that drive tumor growth.

That screening library is now being used to identify potential chemical compounds that can block the activity of a key enzyme, known as a protease, that the novel coronavirus relies on to make more copies of itself in infected cells.

In collaboration with the Argonne National Laboratory at the University of Chicago (another FFRDC), compounds identified in these screens that block the activity of this protease will undergo additional testing and refinement to develop them into potential therapies for COVID-19.

Adapting Cancer Clinical Trials, Launching New Trials

Not surprisingly, the COVID-19 pandemic has had a substantial impact on cancer clinical trials. I have spoken with directors and other staff from NCI-Designated Cancer Centers and this is a serious concern.

As NCI Deputy Director Jim Doroshow, M.D., reported at the board meeting, accrual to NCI-funded treatment clinical trials has dropped by half, a trend that is expected to persist. Accrual to certain trials has continued—for example, those offering life-saving therapies or those for patients who have no other options for therapy—but accrual to most other types of trials has sharply declined.

In response, NCI has worked with FDA and NCI’s clinical trials programs to implement numerous measures to limit disruptions to trials. These steps entail allowing much more flexibility in trial operations, including:

  • directly shipping orally administered drugs being tested in a trial to patients or their local physicians
  • allowing standard testing and assessments that would usually require in-person visits by patients to the trial site to be conducted by a patient’s local physician, who can then send the results to the trial investigators
  • much greater flexibility in complying with requirements written into clinical trials for conducting follow-up tests and reporting data

These are just some of the many changes that have been made to ensure that trials can proceed and produce meaningful data.

In addition to changes to ongoing cancer trials, NCI is working with collaborators to launch clinical studies specific to patients affected by cancer and COVID-19. That includes a “compassionate use” protocol for the drug tocilizumab (Actimra) in cancer patients with COVID-19 who have severe respiratory complications thought to be caused by a hyperactive immune response known as cytokine release syndrome.

The protocol—which will make the drug available to up to 200 patients who are not able to enroll in an ongoing phase III clinical trial of the drug being run by the drug’s manufacturer, Genentech—was written in 4 days by NCI investigators. The eligibility criteria for the study are planned to be adjusted so that both adult and pediatric patients undergoing treatment (including stem cell transplants and immunotherapy) are included. NCI is working with Genentech to get the protocol launched as quickly as possible.

In addition, plans are being finalized for a large clinical cohort study of people with cancer who have COVID-19, involving all of NCI’s clinical trials programs (e.g., NCTN, NCORP).

This study will collect comprehensive documentation from more than 2,000 patients of all ages—such as their cancer type, the treatments they receive, and their symptoms—and follow them for an extended period to better understand the virus’s effect on people with cancer.

This effort will contribute to the serology and genomics studies being conducted at FNLCR as well.

Silver Linings and Next Steps

One thing that stands out to me is that some positive developments have emerged from this otherwise terrible situation.

Among them, we have seen that telehealth is having its moment. As I said at the meeting, researchers involved in implementation science will have a unique opportunity to analyze the impact that telehealth has had on our ability to manage patient care during this pandemic and how telehealth can be most effectively used, and expanded, going forward.

I predict that those being treated for cancer are going to like having some of their care delivered by telehealth, and that many will want to continue using telehealth for some aspects of their care long after the pandemic has ended.

It’s also been inspiring to witness how quickly government health agencies can move when we really need to. New research efforts have been developed and launched with remarkable speed. Processes that can take months or longer have happened sometimes in a matter of days.

As we heard during the board meeting, NCI-Designated Cancer Centers have also taken bold and fast action. Many have already launched clinical trials involving cancer patients with COVID-19, on their own or in collaboration with other cancer centers.

In my opinion, we have learned some important lessons that will change, for the better, how we plan and conduct research and how we care for patients.

As NCI continues our work to make progress in cancer research while also contributing to the global effort to address COVID-19, we will continue to use many communication channels to keep the community informed of our activities. That includes more information on the initiatives described here and others, and the evolving impact of this pandemic on the research community, including a high-priority group for NCI: investigators who are early in their careers.

In the meantime, please stay safe. And please continue to follow directives from public health officials on physical distancing and other measures that will help us to flatten the curve of this pandemic—and, hopefully soon, allow us to begin to emerge from it.

“At NCI, A Robust and Rapid Response to the COVID-19 Pandemic” was originally published by the National Cancer Institute.