A unique two-drug immunotherapy combination first evaluated at Roswell Park Comprehensive Cancer Center as an approach for treating some cancers will soon be available to cancer patients with COVID-19 through a clinical trial at Roswell Park. The U.S. Food and Drug Administration has authorized clinical researchers at the center to conduct a study assessing the safety and effectiveness of giving both rintatolimod and interferon alfa to cancer patients with COVID-19, the disease caused by the novel coronavirus. The study is one of very few worldwide to repurpose an experimental cancer therapy as treatment for COVID-19.
This is exciting and noteworthy science. It's a rare example of a concept for COVID-19 therapy that emerged from academic researchers rather than a pharmaceutical company, and it was a Roswell Park team that looked at the way these two drugs work and saw a possibility for them to enhance each other's effects -; first against cancer and now as a possible treatment for COVID-19."
Candace S. Johnson, Ph.D., Roswell Park President and CEO
Pawel Kalinski, MD, Ph.D., Vice Chair for Translational Research at Roswell Park, was the first researcher to propose giving these two immune-modulating drugs in combination as treatment for cancer, and is scientific lead on five clinical studies in progress or in development assessing the combination in patients with solid-tumor cancers including breast and colorectal cancer. He and clinical principal investigator Brahm Segal, MD, will lead the team investigating whether the two drugs may function effectively together as antiviral agents that could benefit patients with COVID-19.
"There are similarities between cancer and COVID-19, which both manage to avoid activating the interferon pathway," says Dr. Kalinski, who is also Director of Cancer Vaccine and Dendritic Cell Therapies, Rustum Family Professor for Molecular Therapeutics and Translational Research and Professor of Oncology at Roswell Park, and will be scientific lead on the study. "This helps them to go undetected and spread in patients' bodies, and differentiates them from viruses that cause the common cold, which cause rapid symptoms and are rapidly cleared by the immune system."
"We believe that the two agents to be tested in our trial, given together, can activate the missing interferon response in COVID-19-infected cells," he adds. "This would induce protective interferons and other antiviral factors in adjacent cells, stopping the virus from spreading in patients' bodies and generating a synergistic effect that could help cancer patients with mild or moderate COVID-19 to fight the virus before it causes serious damage to the lungs or other organs."
"SARS coronaviruses such as SARS-CoV-2, the virus that causes COVID-19, take hold because they're able to evade the innate immune system," notes Dr. Segal, who is Chair of Internal Medicine and Chief of Infectious Diseases at Roswell Park and Professor at both Roswell Park and the University at Buffalo. "The premise for the trial is that by activating the interferon pathway with these two agents, we may be able to deprive the virus of the ability to replicate, knocking it out before it has a chance to cause severe lung damage or other serious effects. Promising results would pave the way to a larger clinical trial that would include non-cancer patients at high risk for COVID-19 complications."
Patients with cancer and COVID-19 have a risk of severe illness up to five times higher than people without cancer, underscoring the importance of work to develop new treatment options.
Interferon alfa-2b, also known as interferon A (made by various manufacturers), is an FDA-approved drug that has been used in the treatment of some cancers and can boost antiviral immunity. Rintatolimod (brand name Ampligen, manufactured by AIM ImmunoTech Inc.), a form of double-stranded RNA that mimics viral RNA, is an investigational agent that can be recognized by our immune system and activates antiviral defense pathways.
The new clinical trial will test the safety of this combination regimen in patients with cancer and mild to moderate COVID-19, and the extent to which this therapy will promote clearance of the SARS-CoV-2 virus from the upper airway. Earlier published research from Dr. Kalinski's lab has demonstrated that the combination of rintatolimod and interferon alfa-2b shows synergistic activity in preclinical cancer treatment models.
The phase 1/2b study will enroll approximately 40 patients in two stages. Phase 1 will see 12-24 patients receiving both rintatolimod and interferon alfa-2b at escalating doses. Once that initial phase is complete, further study participants will be randomized to two arms, or groups: one receiving the two-drug combination and a control group who will not receive rintatolimod or interferon alfa but will receive best available care.
AIM ImmunoTech has agreed to provide rintatolimod (Ampligen) at no charge for this study.
Additional clinical sites for the study may be added. The new study in cancer patients with COVID-19 will not investigate the effectiveness of this approach as a treatment for cancer; separate studies of that nature are underway at Roswell Park.