Researchers are continuing to study how the combination of Oncolytics Biotech‘s virus-based anti-cancer therapy Reolysin (pelareorep) and Kyprolis (carfilzomib) provides benefits in multiple myeloma patients, according to a recent conference call.
The two experts on the call focused on data from preclinical studies and a Phase 1 clinical trial (NCT02101944) evaluating the two therapies plus dexamethasone in relapsed patients, which showed that proteasome inhibitors such as Kyprolis facilitate Reolysin’s entry, infection, and killing of cancer cells. The results were recently presented at the 61st ASH Annual Meeting in December 2019.
Sponsored by Roth Capital Partners, the call featured two of Oncolytics’ multiple myeloma clinical investigators: Craig Hofmeister, MD, the principal investigator of several Reolysin Phase 1 studies, and Flavia Pichiorri, MD.
Hofmeister is also an associate professor at the Winship Cancer Institute at Emory University School of Medicine, in Atlanta, while Pichiorri works as an associate professor at the City of Hope’s Judy and Bernard Briskin Center for Multiple Myeloma Research, in Duarte, California.
Reolysin is a harmless, naturally occurring virus (reovirus) that was engineered to replicate only in cancer cells, causing their death and releasing virus particles that infect nearby tumor cells. Besides its direct anti-cancer effects, Reolysin also promotes an inflammatory environment and the recruitment of immune cells to the tumor site.
Amgen’s Kyprolis chemotherapy works by blocking the activity of a proteasome — a protein complex responsible for the breakdown of unneeded or damaged proteins — leading to the toxic buildup of faulty proteins inside cells and causing cancer cells’ death.
Kyprolis helps Reolysin enter and infect myeloma cells, the researchers said. This combination boosts anti-tumor immune responses — including those involving a specific type of immune cell called a T-cell — against Reolysin-infected cancer cells.
“I think that carfilzomib promotes [Reolysin] infection by suppressing the innate antiviral response and our data suggest that it does not get in the way of T-cell activation,” Hofmeister said in a press release.
This was based on preclinical evidence showing that Reolysin’s replication in cancer cells was associated with an increase in the levels of PD-L1, whose interaction with PD-1 on the cell surface of T-cells prevents their activation. By preventing this interaction, Opdivo may further boost immune responses against cancer cells.
An open-label Phase 1 trial (NCT03605719) is currently evaluating the safety and effectiveness of combining Reolysin, Kyprolis, dexamethasone, and Opdivo in up to 62 adults with relapsed or refractory multiple myeloma.
The trial’s primary goals are to establish the maximum tolerated dose of Reolysin in the combination and to determine if the combination of Opdivo and Kyprolis leads to a different safety profile than the two therapies used alone. Secondary measures include time to disease progression or death and overall survival.
Researchers also intend to assess the relative roles of Reolysin’s immune-mediated and direct effects in myeloma cells.
The first group of patients receiving a combination of Kyprolis, dexamethasone, and Opdivo is now complete, and escalating doses of Reolysin will be added to the combination in the second group of patients in the coming weeks to determine Reolysin’s maximum tolerated dose.
A third group of patients will be treated with the same dose of Reolysin as in the previous group, combined with Kyprolis, dexamethasone, and Opdivo.
“We are seeing some signs of [pro-inflammatory molecule] release with associated clinical responses,” Hofmeister said.
The call also discussed the competitive market for treatments for refractory multiple myeloma and the lack of available therapies to treat these patients.
“[Reolysin] is the only strategy I see in the market that is completely different and may be able to activate the immune system of these patients,” said Pichiorri, adding that “it would be a salvage therapy for now, but so many patients need a salvage therapy after being refractory to other therapies.”
According to the company, new data from ongoing Reolysin studies in multiple myeloma will be presented at the American Society of Clinical Oncology Annual Meeting in June.