Immunotherapy Trial Opens at NewYork-Presbyterian/Columbia for COVID-19 Patients with Cancer

A drug for cancer patients may not seem like an obvious option to treat COVID-19 patients, but the link between cancers and viruses–the immune system–is providing researchers at the Herbert Irving Comprehensive Cancer Center (HICCC) with new avenues for potential therapies in the fight against COVID-19.

Cancer has many defenses designed to remain undetected by the immune system. Tumor cells hijack the production of cytokines, proteins that immune cells use to signal and coordinate an immune response, cloaking themselves from an attack from the immune system.

Where cancer commandeers cytokines to tamp down the immune system, SARS -CoV-2, the virus that causes COVID-19, can kick the immune system into hyperdrive and release a ‘cytokine storm’ with devastating effects on infected patients.

SARS -CoV-2 enters the lungs and triggers the immune system to recruit immune cells to attack the virus. In some cases, the immune system goes haywire, producing excessive amounts of inflammatory cytokines and recruiting a surge of immune cells that cause hyperinflammation in lung tissue, leading to complications such as adult respiratory distress syndrome (ARDS) and respiratory failure.

Calming the cytokine storm

What if we could stop this cytokine storm from happening? Researchers are looking to target cytokines in finding potential therapies for COVID-19 – several clinical trialshave recently opened using compounds such as sarilumab that block IL-6, one of the key cytokines involved in ARDS.

“We realized that we have a drug that blocks another one of these cytokines – IL-8 – and has already been proven safe in cancer patients,” said Dr. Matthew Dallos, genitourinary oncologist at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center.

Previously, Dr. Dallos and his mentor Dr. Charles Drake, co-leader of the Tumor Biology and Microenvironment Programat the HICCC, opened a clinical trial using an anti-IL-8 compound as part of a combination immunotherapy for prostate cancer. When the COVID-19 pandemic hit New York City, Drs. Dallos and Drake immediately saw an opportunity to test the compound as a potential therapy for the growing numbers of COVID-19 patients – some of them their own.

“Cancer patients appear to have increased risk of getting very sick from SARS-CoV-2 infection, and unfortunately, we are seeing some of our patients being hospitalized for COVID-19,” says Dr. Dallos. “Many clinical trials that are open for new therapies for COVID-19 exclude cancer patients because of their prior cancer therapies or weakened immune systems. We wanted to provide cancer patients with a potential option.”

Dr. Dallos opened the clinical trial last week—the first trial to test an anti-IL-8 compound as a therapy for COVID-19—and has quickly enrolled several patients. Normally, it can take nearly six months to open a clinical trial, navigating through a complex system of approvals, re-writes, and operationalizing enrollment. This trial, however, took only three weeks.

“It’s been an incredible amount of teamwork. Each step of the process has been accelerated to try to stem the tide of this pandemic,” says Dr. Dallos.

First, the drug company providing the compound approved his request to use the drug in this new trial within 24 hours. Then Dr. Dallos began assembling a team to help write the protocol for the trial in less than a week.

“Medical oncologists do a lot of drug development – we are very good at launching and running those kinds of trials and have amazing support from our clinical trials office,” says Dr. Dallos. “But we have no experience writing clinical trials for pulmonary critical care patients, which is essentially how we would classify our COVID-19 patients.”

To help, Dr. Dallos pulled in Dr. Matthew Baldwin, a pulmonologist/critical care physician at NewYork-Presbyterian/Columbia who helped tailor the clinical trial endpoints for these critical patients.

Rapid clinical trial design

Once written, the team submitted the trial to the FDA, who approved it in a week. From there, it was quickly approved by the Columbia University Institutional Review Board within days, which has been meeting daily (instead of bi-weekly) to expedite initiation of COVID-19 clinical trials. A veteran team of research nurses, coordinators, managers and lab personnel under the leadership of Fran Brogan, Director of Clinical Research Operations at the HICCC volunteered to help run this fast-paced clinical trial and have started enrolling patients in record time.

"When there is urgency, people are able to come together and make things happen quickly for our patients," says Dr. Dallos.

Dr. Dallos and his co-investigators hope that this new compound will be a game-changer for cancer patients with COVID-19, and would like to expand the trial to patients without cancer as well. In addition to monitoring patients’ responses, they are diving into the science behind why the new compound works – and potentially in some patients better than others.

The team is working with Dr. David Ho, Clyde '56 and Helen Wu Professor of Medicine at Vagelos College of Physicians and Surgeons, whose laboratory at the Aaron Diamond AIDS Research Center is developing an assay that can measure antibodies against spike proteins, the proteins that protrude from the virus’s surface, allowing it to latch on to the surfaces of lung cells and enter into the lungs. Both the spike protein itself and the antibodies against it have previously been shown to trigger overproduction of IL-8 after coronavirus infection. In addition, in collaboration with the Human Immune Monitoring Core at Columbia, led by Dr. Drake, the team will measure changes in IL-8 and other cytokines that cause the excessive inflammation seen in COVID-19. Together, these studies will allow the team to uncover how the immune system responds to SARS-CoV-2 infection in cancer patients and could help determine which patients are most likely to benefit from anti-IL-8 therapy.

For Dr. Dallos, launching this clinical trial has been a testament to how people across all areas are coming together in the face of this global pandemic.

“We are all learning to do things in new ways,” says Dr. Dallos. “People are very motivated to be a part of this research – they are seeing the effects of this pandemic in their daily lives, in their friends, their families. Everyone wants to help.”