2020 was shaping up to be a busy and exciting year for Pawel Kalinski, MD, PhD, Vice Chair for Translational Research at Roswell Park, and his team at the Center of Immunology. Over the previous seven months, he and his colleagues secured funding for eight clinical trials of different immunotherapy cancer treatments. "All the clinical trials involve what we call 'modulation of the tumor microenvironment.' We have two substances that represent what's known as 'viral mimics.' One substance mimics a double-stranded RNA found in many of the common cold viruses, and the other is a mediator of immune responses to the common cold," says Dr. Kalinski. "Essentially, our efforts are in trying to convince the immune system to fight cancer as aggressively and effectively as it does the common cold."
These clinical trials were starting phase I studies (testing for safety) in prostate and breast cancer and moving into phase II studies (testing for efficacy) in ovarian cancer, breast cancer, colon cancer and melanoma.
The purposes of each trial could be placed into three groups:
- One group of the most advanced trials focuses on patients with advanced cancer to test if the immunotherapy can shrink the overall tumor mass.
- A second group focuses on tumor microenvironments to verify that the new treatments promote the infiltration the tumor with the desirable types of immune cells. Previous studies show that tumors with more immune cells inside of them are more likely to respond to other immunotherapies, radiation and chemotherapy.
- A third group enrolls patients with early-stage, high-risk, triple-negative breast cancer to learn whether the treatment helps more patients achieve complete response to a combination of immunotherapy with chemotherapy, and enhances long-term prognosis.
These studies are performed in collaboration with Drs. Shipra Gandhi, Sarbajit Mukherjee, Christos Fountzilas, Gurkamal Chatta and Igor Puzanov at Roswell Park, as well as collaborators from the University of Pittsburgh and Moffit Cancer Centers. The clinical trials could lead to some groundbreaking results, vastly widening immunotherapy treatment options for patients with aggressive or late-stage cancers. But, like so many other plans for the future, these promising clinical trials were delayed due to the COVID-19 pandemic.
Patients Need Research and Researchers Need Patients
When clinical trials find that a new treatment works better than the existing options, they become the new standard of care, increasing patients' survival and quality of care. But without enough patients willing to participate, clinical trials cannot happen, and the patient population has been greatly reduced during the COVID-19 pandemic.
"The number of cancer patient visits has decreased, at some hospitals, by 30% to 40%. These are the patients that already have cancer. Many patients seem to be more concerned about the coronavirus than they are about their existing cancer. That's worrisome because delays in treatment can affect a treatment's effectiveness. Of course, efficacy is our primary concern when a patient decides to delay their treatment, but research is an important aspect of treating cancer that has been affected, as well," says Dr. Kalinski. "We've had to suspend several of our key clinical trials because fewer patients are willing and eligible to participate, with fewer patients coming to the hospital. A second problem we face as researchers is that we have not been getting a steady supply of cancer tissues to use in testing new drug combinations against some cancers versus others.
"It's very rare that someone has a great idea for an anti-cancer drug, and this idea is proven to be effective in treating cancer at large. It takes time to understand how patients respond to the treatment. To develop new treatments effectively, we need collaboration between the lab staff, clinical teams and patients to properly understand how this treatment is being tolerated and its effectiveness against cancer."
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Shifting Resources to COVID-19
Because of their disease and the effects of their treatment, many cancer patients are immunocompromised, especially those on chemotherapy or who had recent surgery, making them more susceptible to viruses like COVID-19. As many states, including New York, begin their reopening process, there is hope that cancer patients will return to their regular treatment schedules. Until a COVID-19 vaccine is developed, the next best thing that would bring peace of mind to many high-risk patients would be a treatment for a COVID-19 infection. This is something Dr. Kalinski's team is now shifting their effort towards.
"Coronavirus infections like COVID-19, are similar to cancer, in that they do not send alarm signals to the rest of the body when the infection occurs, and they do not show symptoms until they are already very prevalent in the body, similar to a tumor. By the time they starts doing damage to our tissues, it's typically very late, and our immune system isn't very effective at fighting them," says Dr. Kalinski.
Early on in the COVID-19 pandemic, Dr. Kalinski's team found data showing two of the anti-cancer drugs (rintatolimod and interferon alfa) used in clinical trials to activate immune responses to cancerous tumors, trigger similar defense mechanisms against coronaviruses.
While practicing proper lab safety, and by splitting the work into morning and evening shifts, Dr. Kalinski's team began processing the data that they would need to get approval for a COVID-19 clinical trial.
"We teamed up with our Chief of Infectious Diseases, Brahm Segal, MD, and refocused our research away from cancer, to how we can fight COVID-19. We got to work gathering data to show the Food and Drug Administration (FDA) that we can use the same combination of drugs that we have been using to treat cancer, to help treat cancer patients, who also develop a COVID infection," says Dr. Kalinski.
On May 15, the FDA gave the authorization to begin the study of the safety and effectiveness of giving both rintatolimod and interferon alfa to cancer patients with COVID-19. "As soon as we get back some early safety data, we expect that we will be able to expand the inclusion criteria. We hope the FDA will allow us to move this trial into the general population to treat COVID patients without cancer," says Dr. Kalinski.
Having your work delayed by something completely out of your control like a pandemic, is obviously discouraging. But in the end, for cancer researchers like Dr. Kalinski and his team, finding ways to help those in need — whether through cancer or COVID-19 treatments — is truly what their work is about.
“Coronavirus certainly delayed our work on the development of better treatments of cancer. It seems to be discouraging cancer patients from participating in clinical trials, and worse, from complying with routine cancer screening and cancer care. This is a huge problem affecting our healthcare system and our society,” says Dr. Kalinski. “On the other hand, we’ve been able to pivot and focus on something else that will hopefully help both COVID and cancer patients in the near future. As they say: When life serves you lemons, try making lemonade.”