RE:Myeloma In March 2022 an AACR presentation reported on a completed phase 1b trial evaluating the combination of pelareorep and the proteasome inhibitor bortezomib in relapsed/refractory multiple myeloma patients (ex an immune checkpoint inhibitor like pembrolizumab).
Results from the trial showed that the combination was well-tolerated and led to prolonged progression-free survival (PFS) of over three years in a subset of patients.
Additionally, biomarker data demonstrated increased infiltration of T and NK cells in the tumor immune microenvironment post-treatment. These post-treatment increases in anti-cancer immune cells correlated with both clinical response and changes in T cell clonality, which has previously been identified as a potential predictive biomarker that could increase the likelihood of success in future trials of pelareorep by informing patient selection.
"To see patients resistant to prior therapies achieve multi-year PFS is a remarkable finding that speaks to pelareorep's potential to synergistically combine with anti-cancer agents and provide sustained clinical benefit," said Kevin Kelly, M.D., Ph.D., Associate Professor of Clinical Medicine at the Keck School of Medicine of the University of Southern California and Principal Investigator of the trial. "The observed correlation between clinical response and increases in anti-cancer immune cells in the tumor immune microenvironment is also an important result, as it suggests the studied combination's activity is being driven by pelareorep's immunologic mechanism of action. I look forward to discussing these findings with the clinical community and presenting additional data from the trial at the upcoming AACR meeting."
https://www.oncolyticsbiotech.com/press-releases/detail/562/oncolytics-biotech-announces-phase-1b-data-demonstrating
As background - In earlier pre-cinical studies ONCY showed that ex vivo proteasome inhibitors (PIs) potentiate reovirus replication in circulating classical monocytes, increasing viral delivery to myeloma cells. We found that the anti-viral signals in monocytes primarily rely on the NF-kB activation and that this effect is impaired by the addition of PIs.
Conversely, PIs improved reovirus-induced monocyte and T cell activation against cancer cells.
Based on these preclinical data, ONCY conducted a phase 1b trial of the reovirus Pelareorep together with the PI carfilzomib in 13 heavily pretreated bortezomib-resistant MM patients.
Objective responses associated with reovirus active replication in MM cells, T cell activation and monocytic expansion were noted in 70% of patients.
https://www.medrxiv.org/content/10.1101/2022.03.29.22272857v1
https://clinicaltrials.gov/ct2/show/NCT02514382