The open-label, dose escalation study (NCT03605719) will evaluate the safety and best dosing schedule of Oncolytics Biotech’s Reolysin when given with Amgen’s Kyprolis, Bristol-Myers Squibb’s Opdivo, and dexamethasone to adults with relapsed multiple myeloma.
The study’s primary goals are to establish the maximum tolerated dose of Reolysin in the combination. Secondary measures include time to disease progression, overall survival, and the development of inflammation in the tumor microenvironment, including biomarker responses indicative of inflammation. Patient recruitment, for a maximum of 62 participants, is ongoing (find more information here). The trial is being conducted at Atlanta’s Emory University.
Reolysin is a harmless, naturally occurring virus (reovirus), modified to replicate only in cancer cells, causing their death and releasing virus particles that infect nearby tumor cells. It also recruits immune cells into the tumor site, favoring an inflammatory environment. Reolysin was designed for the treatment of both solid tumors and blood cancers via intravenous infusion.
Opdivo is a type of therapy known as a checkpoint inhibitor. It binds to a protein called PD-1 on immune T-cells to prevent their interaction with PD-L1 on cancer cells. Such binding of PD-L1 to PD-1 is used by cancer cells to evade immune attack.
Kyprolis is a proteasome inhibitor. It stops the protein clearance process occurring in cellular structures called proteasomes, which leads to the buildup of faulty proteins and causes malignant cells to die.
The trial is based on results from the NCI 9603 study (NCT02101944) showing that combining Reolysin with Kyprolis eliminated multiple myeloma cells and induced inflammation in the tumor microenvironment, with overexpression of PD-L1 in immune cells.
The findings suggest that the combination of Reolysin and Kyprolis makes patients more receptive to immune checkpoint inhibitors like Opdivo.
“My hope is this study leads not only to an effective combination dosing schedule but provides quantitative data describing the expression of PD-1, along with correlative studies that reveal the roles of both immune-mediated and direct cytotoxic myeloma cell killing,” Craig Hofmeister, MD, who is leading the trial, said in a press release.
Rita Laeufle, Oncolytics’ chief medical officer, said she is “excited for the potential of the immune and biomarker data” coming from this trial.
Besides Opdivo, Reolysin is being assessed with Merck’s Keytruda (pembrolizumab) in multiple myeloma, and with Roche’s Tecentriq (atezolizumab) in neoadjuvant breast cancer. Keytruda and Tecentriq are also checkpoint inhibitors.
Altogether, these studies “will provide further evidence that pelareorep has the potential to expand the use of checkpoint inhibitors by priming tumors’ cells,” Laeufle said. Laeufle said that confirming Oncolytics’ biomarkers increases the likelihood of success in registrational studies — those serving as the basis for product approval — thereby making Reolysin more attractive to potential partners.
In May 2017, the U.S. Food and Drug Administration granted fast track designation to Reolysin as a potential treatment for metastatic breast cancer. It has also been designated an orphan drug for its therapeutic potential in glioblastoma, ovarian cancer, and pancreatic cancer.