Combination of Reolysin, Opdivo, and Standard of Care to Be Tested in Phase 1 Trial for Multiple Myeloma

A combination of Oncolytics Biotech’s investigational therapy Reolysin (pelareorep) with anti-cancer medication Opdivo (nivolumab) and standard of care will be tested in patients with relapsed or refractory multiple myeloma.

The open-label Phase 1 trial (NCT03605719) is not yet recruiting, but the first of an estimated 62 patients is expected to be enrolled by the end of 2018.

Reolysin is a naturally occurring virus (reovirus) that does not cause disease, engineered to replicate only in cancer cells. It is delivered intravenously (directly into the blood) and is intended for the treatment of both solid tumors and blood cancers. Reolysin’s replication in cancer cells causes their death, releasing virus particles that infect nearby tumor cells.

The treatment’s therapeutic effect is also due to the recruitment of immune cells into the tumor site, promoting an inflammatory environment. This turns “cold” tumors — those that are devoid of immune cells — into “hot” tumors.

Bristol-Myers Squibb’s Opdivo is a type of therapy that activates immune cells once they are already inside the tumor. It binds to a protein called PD-1 on immune T-cells to prevent their binding to PD-L1 on cancer cells. The binding of PD-L1 to PD-1 is used by cancer cells to evade immune attack.

Specifically, the research will determine the safety of the combination, when added to standard of care, for relapsed or refractory myeloma patients. Secondary measures include time to disease progression, time until disease progression or death from any cause, and overall survival.

In addition, researchers will also assess the development of inflammation in the tumor microenvironment and examine Opdivo’s benefits in a population of patients who produce the PD-L1 factor.

Patients may also receive the immunomodulatory medication Pomalyst (pomalidomide, by Celgene, marketed as Imnovid in Europe) once the safety of the initial combination is demonstrated. Pomalyst is currently indicated in combination with dexamethasone for myeloma patients whose disease worsened after at least two prior anti-myeloma treatments.

“This study expands on our strategy of investigating the importance of systemic [Reolysin] administration followed by checkpoint blockade in selected indications,” Matt Coffey, Oncolytics’ president and CEO, said in a press release.

Coffey also said Opdivo is the third checkpoint inhibitor being studied by Oncolytics in clinical studies after Tecentriq (atezolizumab, by Genentech) in breast cancer and combinations of Reolysin with Keytruda (pembrolizumab, by Merck) in myeloma and pancreatic cancer.

Overall, the study will contribute to an increasing body of data on the combination of Reolysin with checkpoint inhibitors, Coffey added. “Importantly, it will not only help us demonstrate the specific role of [Reolysin] in promoting an inflamed phenotype, it should also help us understand how the virus may promote responses to checkpoint blockade in cold tumors, thus potentially expanding the commercial potential of these immunotherapies.”

The study will be led by Craig C. Hofmeister, MD, at Emory University, and Douglas Sborov, MD, at the University of Utah.

Reolysin “has demonstrated safety and the ability to turn cold tumors hot,” according to Hofmeister. “We plan to capitalize on this inflamed phenotype by infusing [Reolysin] and the PD-1 checkpoint inhibitor, [Opdivo], together.”

Oncolytics will provide Reolysin, while Emory University has secured supply of Opdivo. Final study design and other details will be revealed once patient enrollment begins.

Reolysin was granted fast track designation by the U.S. Food and Drug Administration as a potential treatment for metastatic breast cancer. It was also designated an orphan drug by the FDA for its potential to treat glioblastoma, ovarian cancer, and pancreatic cancer.