Oncolytics Biotech (NASDAQ: ONCY) (TSX: ONC) has announced a publication of phase 1 clinical trial data demonstrating the clinical benefit of their immuno-oncolytic virus pelareorep in combination with the medications FOLFIRI and bevacizumab for the treatment of colorectal cancer.
The article, “Elucidation of Pelareorep Pharmacodynamics in a Phase I Trial in Patients with KRAS Mutated Colorectal Cancer,” was published in the peer-reviewed journal Molecular Cancer Therapeutics.
The phase 1 clinical trial evaluated the anti-cancer efficacy of the drug combination in 36 patients with KRAS-mutated colorectal cancer. According to Oncolytics’ press release, “the combination of FOLFIRI, bevacizumab and pelareorep was well tolerated, with promising signals of efficacy.”
Six patients receiving the “recommended phase 2 dose” experienced an overall response rate of 50% and median overall survival of 25.1 months “which compares favorably to the historical OS of 13.5 months (an 86% improvement).” Of the 30 patients that completed the trial, “6 (20%) had a partial response (PR) and 22 patients (73.3%) had stable disease (SD) as their best response, for a clinical benefit rate (PR +SD) of 93.3%.”
Chief Medical Officer of Oncolytics Biotech Rita Laeufle, MD, PhD, stated, “Pelareorep combined with FOLFIRI, bevacizumab triggers a robust adaptive immune response, highlighting a unique pattern of dendritic cell maturation followed by CD8 T cell activation that was observed after every dose of pelareorep.”
“Importantly, we have received great interest from key opinion leaders who are eager to work with pelareorep in gastrointestinal cancers, and this paper supports that interest. Our biomarkers of T cell clonality and CEACAM6, along with these promising efficacy findings, have allowed us to craft a clear clinical strategy in gastrointestinal cancers, and we look forward to providing updates on those plans in the near future,” Dr. Laeufle continued.
Pelareorep is an intravenously-administered oncolytic virotherapy consisting of “non-pathogenic, proprietary isolate of the unmodified reovirus,” a virus that occurs naturally within the environment and that is being applied by Oncolytics Biotech for the treatment of hematological malignancies and solid tumors. Oncolytics Biotech has evaluated the therapy in multiple studies including the phase 1 trial addressed by this article.
By infecting and lysing cancerous cells, the virus promotes inflammation at the site of tumors that may lead to innate and adaptive anti-cancer immune responses. Pelareorep is currently being evaluated for the treatment of cancer in combination with immune checkpoint inhibitors and other immunotherapeutics, with which the virus is thought to mediate a synergistic anti-cancer effect.
According to Oncolytics Biotech, the phase 1 trial demonstrated evidence of “an adaptive immune response occurring after each cycle of pelareorep treatment,” including the maturation of a population of antigen-presenting cells known as dendritic cells, an increase in the number of CD4+ and CD8+ T lymphocytes, and the activation of CD8+ T cells.”
The press release stated that these “dramatic immune responses were only seen after pelareorep administration and not with the other medications alone, strongly suggesting that pelareorep is influencing these responses.”
Biopsies of tumors from patients in the study “revealed replicating virus (pelareorep),” indicated that the virus-based treatment had successfully transmitted from the site of administration to that of the tumor, and that the virus was replicating within the tumor.
In addition to oncolytic virotherapy, solid tumor treatment approaches incorporating targeted antibodies and engineered lymphocytes are also under development.
An antibody inhibitor of the cell surface protein CD39 is being evaluated by Surface Oncology and Merck and a combination of the checkpoint inhibitors Opdivo and Yervoy has shown promise for the treatment of metastatic non-small cell lung cancer.
Adaptimmune is exploring the anti-cancer activity of SPEAR T cells and NantKwest is evaluating the safety and efficacy of a natural killer cell-based therapy which has shown promise for the treatment of pancreatic cancer.