The attenuated vaccinia virus, GL-ONC1, demonstrated safety and clinical benefit when delivered intravenously with concurrent chemoradiation therapy in patients who have locoregionally advanced head and neck carcinoma (LA-HNC).
Loren K. Mell, MD
The attenuated vaccinia virus, GL-ONC1, demonstrated safety and clinical benefit when delivered intravenously with concurrent chemoradiation therapy in patients who have locoregionally advanced head and neck carcinoma (LA-HNC), according to a phase I study, making this class of therapies an interesting potential treatment strategy.
The trial was the first to establish the safety of intravenous (IV) GL-ONC1 in patients who have LA-HNC, undergoing concurrent chemoradiation therapy.
“This was a phase I trial primarily designed to test for toxicity and feasibility. We were trying to determine if there is still a potential to cure head and neck cancer by adding an oncological vaccinia to the standard regimen of chemoradiation. To do that, we needed to get patients through that toxic regimen and then see if there is enough efficacy to warrant testing in a phase II study,” said Loren K. Mell, MD, chief, Head and Neck Malignancy Service, associate professor, University of California, San Diego, in an interview withTargeted Oncology.
The trial consisted of 19 patients who were evaluated from May 2012 to December 2014. Seventy-eight percent of the 18 patients completing chemoradiation therapy had 3 cycles of cisplatin, while 22% had 2 cycles. The median follow-up was 17 months, and the Kaplan-Meier estimate of 1-year progression-free survival was 82%. In addition, the overall survival was 87%, and the maximum-tolerated dose was not reached.
According to Mell, this study was the first to demonstrate that GL-ONC1 could be delivered intravenously to patients receiving chemotherapy and radiation simultaneously. He and his team were able to get patient outcomes, when comparing success rates to historical rates.
Toxicities grade 2 or higher consisted of rigors (47% of patients), thrombocytopenia (32%), and fever (26%). A rash of grade 1 or higher was reported in 21% of patients; it was confirmed to be viral in origin in two patients. Mell stated that the rash was pox-like, but it was short-lived and mild. Viral shedding was not detected on urine or oral swab 1 to 2 days post infusion of GL-ONC1.
According to Mell, flu-like symptoms were experienced a few hours after administration of the vaccine as well. “GL-ONC1 is a genetically modified vaccinia that is related to cowpox, so it does not naturally infect humans. That makes it desirable for this purpose. We believe the safety profile to be good. There was prior evidence that showed it was safe to deliver; however, we were unsure that, if we delivered it at the same time as chemotherapy and radiation, it would be a tolerable regimen for patients to undergo. Nevertheless, it was tolerable,” he said.
Mell thinks that oncolytic viruses are a particularly interesting class of therapies. He noted many studies in preclinical models demonstrating that these drugs are effective and may increase the efficacy of radiation and chemotherapy. Patients with LA-HNC tend to present in stage IV of the disease, and their tumors are either very large, or they advance in the lymph nodes in the neck. Mell and his colleagues are aware that outcomes for standard chemotherapy are not very great, especially those associated with smoking and drinking, so they would like to improve on that.
“The next step is a phase II clinical trial designed to test the therapy against a control arm versus the approach we used in this trial to see if their outcomes are better. Those are usually larger trials that enroll 120 patients, while the phase I study only included 19 patients,” concluded Mell.