Recent Trial Data on Tebentafusp in Metastatic Uveal Melanoma
Source: Onc Live, July 2022
Ryan Sullivan, MD: Now is a good time to talk a little about the clinical trial data, and then we can have a discussion about the toxicities and the management of the toxicities. One of the toxicities, as you mentioned, is cytokine release syndrome, which requires hospitalization. It’s important to note that the clinical trial that led to the approval of this agent was built on phase 1 and 2 testing.
The initial trial of this agent was in cutaneous melanoma in patients who had surgical resection. It was presented by one of our colleagues, Mark Middleton, at an AACR [American Association for Cancer Research] meeting about 6 years ago. I remember watching him give this talk and thinking, “This is a really neat thing, but that’s a weird population to start looking at a drug like this.” It fit in with the field of melanoma, where there were a lot of adjuvant studies of vaccines, and this was maybe a weird kind of vaccine. Obviously, it isn’t that. It’s a very different type of molecule. But soon after, it transitioned to being looked at in both cutaneous and uveal melanoma.
To your point, the gp100 peptide is much more consistently expressed in uveal melanoma than in cutaneous melanoma for reasons that probably are immunologic. Cutaneous melanoma is typically so genetically altered by UV or radiation that it has to come up with all kinds of mechanisms to get around the immune system, whereas uveal melanoma is much less genetically disturbed. It’s probably better able to remain differentiated as opposed to the dedifferentiated subtypes that we see in cutaneous melanoma. With that expression of the protein, it seemed like patients with uveal melanoma are doing better. But interestingly, doing better doesn’t mean high response rates.