Reolysin, an investigative drug to be used in combination with carboplatin and paclitaxel in patients with lung cancer, will soon undergo phase 2 studies to evaluate its efficacy.
Oncolytics Biotech Inc has announced that the Cancer Therapy & Research Center at the University of Texas Health Science Center (CTRC) has started patient enrolment in a U.S. Phase 2 clinical trial using intravenous administration of Reolysin.
“There are significant similarities between SCC lung and SCC head and neck cancers,” said Dr. Karl Mettinger, Chief Medical Officer for Oncolytics.
Oncolytics Biotech is observing clinical benefit of Reolysin in metastatic lung lesions used as a monotherapy or in combination with paclitaxel and carboplatin.
Reolysin, the company’s proprietary formulation of the human reovirus, has been demonstrated to replicate specifically in tumour cells bearing an activated Ras pathway.
Activating mutations of Ras and upstream elements of Ras may play a role in greater than two thirds of all human cancers.
Reolysin may represent a novel treatment for Ras activated tumour cells and some cellular proliferative disorders.
Reovirus, an acronym for Respiratory Enteric Orphan virus, is generally believed to inhabit the respiratory and bowel systems in humans. Reovirus is found naturally in sewage and water supplies.
By age 12, half of all children show evidence of reovirus exposure and by adulthood, most people have been exposed.
However, the disease is non-pathogenic, meaning there are typically no symptoms from infections.
The link to its cancer-killing ability was established after the reovirus was discovered to reproduce well in various cancer cell lines.
Tumours bearing an activated Ras pathway are deficient in their ability to activate the anti-viral response mediated by the host cellular protein, PKR.
Since PKR is responsible for preventing reovirus replication, tumour cells lacking the activity of PKR are susceptible to reovirus replication.
As normal cells do not possess Ras activations, these cells are able to stop reovirus infection through normal PKR activity.
In tumour cells with an activated Ras pathway, reovirus is able to freely replicate and eventually kill the host tumour cells.
As cell death occurs, progeny virus particles are then free to infect surrounding cancer cells. This cycle of infection, replication and cell death is believed to be repeated until there are no longer any tumour cells carrying an activated Ras pathway available.
More recently, Oncolytics has discovered that tumour antigens generated by this viral oncolysis may educate the immune system to recognize and kill tumour cells.
The activation of the Ras pathway can be mimicked in non-cancerous cells by treating these cells with the chemical 2-aminopurine (2-AP) which prevents the activation of PKR.
The trial (REO 021) is a single arm, open-label, Phase 2 study of Reolysin given intravenously with paclitaxel and carboplatin every three weeks. Up to 55 patients are expected to be treated in this trial.
Eligible patients include those with metastatic stage IIIB, or stage IV, or recurrent squamous cell carcinoma of the lung who are chemotherapy naïve for their metastatic or recurrent cancer.
The primary objective of the Phase 2 trial is to assess the antitumor effect of the treatment regimen in the study population in terms of objective response rates. The secondary objectives are to assess progression-free survival and overall survival for the treatment regimen in the study population; to determine the proportion of patients receiving the above treatment who are alive and free of disease progression at six months; and to assess the safety and tolerability of the treatment regimen in the study population.
This trial is part of a broad preclinical and clinical collaboration with the CTRC that will involve up to five, open-label, Phase 2 studies exploring the use of Reolysinin combination with chemotherapy for various cancer indications.
The American Cancer Society estimates that in 2009, there were approximately 219,440 new cases of lung cancer.
Approximately 85% of all lung cancers are classified as non-small cell lung cancer (NSCLC); squamous cell carcinomas account for 25-30% of all lung cancers.
Lung cancer is by far the leading cause of cancer death among both men and women. There were an estimated 159,000 deaths from lung cancer in 2009, accounting for around 28% of all cancer deaths.
More people die of lung cancer than of colon, breast, and prostate cancers combined.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics.
Oncolytics’ clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using Reolysin, its proprietary formulation of the human reovirus.
The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the nation’s leading academic research and treatment centers, serving more than 4.4 million people in the high-growth corridor of Central and South Texas including Austin, San Antonio, Laredo and the Rio Grande Valley.
CTRC is one of a few elite cancer centers in the country to be named a National Cancer Institute (NCI) Designated Cancer Center, and is one of only three in Texas.
The CTRC Institute for Drug Development (IDD) is internationally recognized for conducting the largest oncology Phase I clinical drug trials program in the world, and participates in the clinical and/or preclinical development of many of the cancer drugs approved by the U.S. Food & Drug Administration.