Video

Oncolytic Viruses: Melanoma and Bladder Cancer

Transcript:Mark A. Socinski, MD: I want to shift gears a little bit. I want to ask Howard about oncolytic virus therapy.

Howard L. Kaufman, MD: So, the concept of oncolytic viruses is that certain viruses have innate properties, or can be engineered to selectively replicate in cancer cells. And so, the first virus that achieved FDA approval was for melanoma in October of 2015 was using a herpes simplex type 1 virus, which causes the typical fever blister. The virus has been engineered, so the neurovirulence factors are removed. And, it also encodes GM-CSF (granulocyte-macrophage colony-stimulating factor) to help to generate an immune response. This is actually given directly into the tumor. The way we give this is that patients who have accessible lesions come in the office. We actually measure the size of the tumor on a given day, and we can inject up to 4 cc’s of this, at any given time. We start with a low dose and allow the seronegative patients to convert. Then, 3 weeks later, we give a higher dose, repeated every 2 weeks.

In what was really the first prospective-randomized phase III study, the treatment with talimogene laherparepvec, or TVEC, did show an improvement in both durable and objective response rates. There was also improvement in progression-free survival and overall survival, although the overall survival benefit didn’t reach statistical significance. Nonetheless, a lot of patients experienced significant improvements. And, I think, that oncolytic viruses have a lot of potential for taking T-cell poor tumors, bringing in T cells, to make them T-cell rich. I think that gets us into combining TVEC with other things that can expand T cells. Many of those combination studies are underway, and we anticipate reporting out on some of those very soon with some pretty interesting results.

In terms of toxicities, we see very little. There’s some low-grade fever and chills, and we’ve been seeing sometimes some injection site reactions. This is usually pretty well tolerated with some Tylenol on the day of the injections, so, it’s another approach. It’s been particularly useful in elderly patients, patients who may have other comorbid conditions, so they can’t really tolerate some of the more extensive therapies. And interestingly, in the phase III study, we had close to an 11% complete response rate. Even visceral lesions, other lesions that weren’t injected, did go away. It adds another therapeutic option. I think future studies are going to be doing these combinations, and extending this into other types of cancer.

Mark A. Socinski, MD: And there are some efforts in bladder cancer, right?

Dean F. Bajorin, MD: There are. Actually, there’s a replicating adenovirus, CG0070, with the same kind of approach. This has a GM-CSF vector that is inserted. Interestingly enough, there was a study just looking at whether the virus got into the tumors, and whether there was GM-CSF that was elicited afterwards. It actually replicated in the bladder. Although it was a study looking at really an analysis of whether it worked or not in terms of GM-CSF, it actually did cause substantial regression of the tumor, over 40%. Now, this is in bladder non-muscle invasive disease. So, this is that BCG-unresponsive space I was talking about before, where there are no therapies and which you don’t really need a randomized controlled trial. The FDA will accept a non-comparator trial. CG0070 is in a study now in the United States to see if there’s benefit.

Mark A. Socinski, MD: And with atezolizumab being approved, do you see room for combination therapies down the road?

Dean F. Bajorin, MD: That’s where we’re headed. If you take a look at a lot of these tumors, there are a lot of tumors that do not have infiltration. And the question is, how can you provide that impetus, the recognized antigen one way or another, whether it’s injection of a virus—in fact, we’re looking at Newcastle virus at our center—or whether it’s by radiation therapy? The breast groups are using cryoablation and combining it as well, so yes.

Transcript Edited for Clarity

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