Loren K. Mell, MD
The attenuated vaccinia virus GL-ONC1 demonstrated safety and clinical benefit when delivered intravenously with concurrent chemoradiation therapy for patients with locoregionally advanced head and neck carcinoma (LA-HNC) in a recent phase I study.
This is the first trial to establish the safety of IV GL-ONC1 for patients with LA-HNC undergoing concurrent chemoradiation therapy.
Nineteen patients were included in the trial from May 2012 to December 2014. Of the 18 patients completing chemoradiation therapy, 78% had 3 cycles of cisplatin and 22% had 2 cycles. With a median follow-up of 17 months, the Kaplan-Meier estimate of 1-year progression-free survival was 82% and overall survival was 87%. The maximum-tolerated dose was not reached.
Grade 2 or higher toxicities included rigors (47% of patients), thrombocytopenia (32%), and fever (26%). A grade 1 or higher rash was reported in 21% of patients. The rash was confirmed to be viral in origin in two patients. No viral shedding was detected on urine or oral swab 1 to 2 days post infusion of GL-ONC1.
To further understand these findings, OncLive
spoke with lead study author Loren K. Mell, MD, chief, Head and Neck Malignancy Service, associate professor, University of California, San Diego.OncLive: What was the goal of the trial?Dr Mell
: This was a phase I trial primarily designed to test for toxicity and feasibility. We were trying to determine if, for patients with advanced head and neck cancer, there is still potential for a cure 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.What were the most significant findings?
We were able to deliver IV vaccinia. This was the first study to demonstrate that this particular agent could be delivered intravenously to patients who were receiving chemotherapy and radiation at the same time. We found that we could successfully deliver that, and we were able to get outcomes for patients when we compared their success rates to historical trials.What impact will these findings have?
As a class of therapies, oncolytic viruses are an interesting strategy. There are certainly a number of studies in preclinical models that demonstrate that it is effective and can help radiation and chemotherapy work better against cancers. These patients generally have stage IV head and neck cancer. Their tumors are either very large or have advanced into the lymph nodes in the neck. The outcomes for standard chemotherapy and radiation, especially those associated with smoking and drinking, are not great. We would like to improve on that. This is a leading strategy to try and do that.What are the main toxicities associated with this vaccinia virus?
A toxicity that we encountered that can be attributed directly to the virus was a pox-like rash, which was short-lived and mild. Patients also experienced flu-like symptoms for a few hours after the vaccine was administrated. Beyond that, we did not detect any shedding of the virus. 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.What are the next steps in this research?
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.What are some of the biggest challenges in treating head and neck cancer?
The standard treatment protocol for radiation lasts approximately 7 weeks with generally about six treatments per week. Chemotherapy has its own set of toxicities, and most patients who are treated get very sore throats and tend to lose weight. It is a grueling treatment regimen, but it’s effective. We would like to seek treatment methods that are effective but less toxic. When we add treatment like this, it may increase toxicities; however, we don’t want to scale back on things that we know are effective until we have something better to replace them with.