NCI-9603 is a single arm, open-label translational study to assess the therapeutic combination of intravenously-administered REOLYSIN® with dexamethasone and carfilzomib in patients with relapsed or refractory myeloma. Patients will receive treatment on days 1, 2, 8, 9, 15 and 16 of a twenty-eight day cycle, to be repeated in the absence of disease progression or unacceptable toxicity. Approximately twelve patients will be enrolled in the study. The primary objectives include measuring reovirus replication, safety, and tolerability. Secondary objectives include examining objective response, duration of response, clinical benefit, progression-free survival, and time to progression. Other objectives include the measurement of immunologic correlative markers.
Initial findings from the study were presented by Oncolytics collaborators at the 15th International Myeloma Workshop in Rome, Italy. 100% of patients (8 of 8) experienced an objective response as measured by changes in blood monoclonal protein. Of these, 2 patients had a very good partial response (VGPR), 3 patients had a partial response (PR) and 3 patients had a minor response (MR). The collaborators and others were noted to have conducted preclinical investigations that demonstrated that the combination of REOLYSIN® and carfilzomib synergistically increased the killing of multiple myeloma cells. This provided the clinical rationale for this study. In this study, the combination of carfilzomib and REOLYSIN® produced a significant (p=0.005) increase in caspase-3, a marker associated with apoptotic cell death. The researchers also determined that the combination of REOLYSIN® and carfilzomib increases infiltration of CD8+ T-cells and significantly (p=0.005) upregulates PD-L1. The investigators concluded that these findings necessitated continued investigation, and suggested that the addition of a PD-1 or PD-L1 inhibitor may further optimize the REOLYSIN® and carfilzomib regimen.
The study is being sponsored and conducted by the US National Cancer Institute (NCI). Final results from the study remain pending.