First Patient Dosed in IRENE Trial Testing Immunotherapy-Oncolytic Virus Combo

First Patient Dosed in IRENE Trial Testing Immunotherapy-Oncolytic Virus Combo

The first participant has been dosed in the Phase 2 clinical trial IRENE, which is evaluating Incyte‘s immunotherapy retifanlimab in combination with the oncolytic virus pelareorep, by Oncolytics Biotech, as a treatment for locally advanced or metastatic triple-negative breast cancer (TNBC).

The trial (NCT04445844) is currently recruiting patients at the Rutgers Cancer Institute of New Jersey, and is planning to also enroll participants at The Ohio State University Comprehensive Cancer Center. Additional information is available here.

“The paucity of treatment options in metastatic triple-negative breast cancer combined with its aggressive clinical behavior results in a poorer prognosis when compared to other subtypes of breast cancer,” Mridula George, MD, a medical oncologist at Rutgers Cancer Institute of New Jersey and investigator on the clinical trial, said in a press release.

“I’m looking forward to getting this study underway to potentially make an impact in the lives of patients affected with metastatic triple-negative breast cancer,” George added.

The body’s immune system has the natural capability to destroy cancer cells. But cancer cells often evolve strategies for avoiding immune-mediated destruction.

Retifanlimab (INCMGA00012) is an antibody therapy that works by inhibiting PD-1, a protein that is commonly expressed by cancer cells to help them escape the immune system. By blocking this protein, retifanlimab is designed to allow the immune system to more effectively kill cancer cells.

Meanwhile, pelareorep is an oncolytic virus — a virus that is able to infect and kill cancer cells. Specifically, pelareorep is a form of reovirus, a type of virus commonly found in environmental water. In humans, infection with unmodified reovirus is typically mild, with symptoms similar to the flu or the common cold. Scientists have engineered pelareorep such that it is able to infect and kill cancer cells, but it cannot effectively infect and kill healthy cells.

In addition to this direct cancer cell-killing effect, pelareorep also is thought to stimulate an anti-cancer immune response. That is the theoretical basis for why it might be particularly effective in combination with retifanlimab.

The IRENE clinical trial — fully named INCMGA00012 and the oncolytic virus pelareorep in metastatic triple-negative breast cancer — is a single-arm, open-label study, meaning that all participants will get the same active treatment (there will be no placebo).

The study seeks to enroll about 25 women, ages 18 and older, with TNBC that is locally advanced and unresectable — meaning it can’t be removed surgically — or is metastatic, which means the cancer has spread from the breast to elsewhere in the body.

The participants will be given pelareorep intravenously (into-the-vein) on days 1, 2, 15, and 16 of 28-day treatment cycles; retifanlimab will also be given on the third day of each cycle. Treatment will continue until disease progression, such as tumor growth, is observed.

The main goals of IRENE are to determine the percentage of participants who have an objective response to treatment, which means a measurable decrease in tumor size. The trial also will evaluate the combination treatment’s safety and tolerability. Other endpoints, including survival, quality of life, and immunological measurements, also will be assessed.

“This is an exciting study to evaluate the role of immunomodulation in the tumor microenvironment as a treatment option,” George said.

The IRENE trial is being co-sponsored by Oncolytics, the Rutgers Cancer Institute of New Jersey, and Incyte.