Kaposi sarcoma is a cancer, it’s a vascular tumour that’s caused by a virus and it affects people with and without HIV. So the standard therapies that are available for this condition are mainly chemotherapies and some immunomodulatory agents. There have been very few therapies that have been explored for Kaposi sarcoma and those that are T-cell sparing, because it’s a tumour that’s really driven by immune depletion, immune dysregulation. So we were very excited to explore CDK4/6 inhibitors which have a lot of in vitro studies using KSHV infected B-cells and endothelial cells. There has been a lot of data to suggest that CDK4/6 inhibitors might actually affect the virus that drives KS in these cell lines.

So we developed a study using abemaciclib in Kaposi sarcoma in participants with both HIV and without HIV. That’s the study that I’ll be presenting at ASCO this year.

What was the methodology?

We enrolled participants with and without HIV who had confirmed Kaposi sarcoma. They were required to have at least five lesions on their skin because it’s a disease that affects the skin but it can also affect internal organs. It’s a phase I/II study because this drug hasn’t been used in this indication before. So the first phase was ensuring that we established a viable dose, so we used the standard approved dose of 200mg twice a day orally in participants with KS. We enrolled participants who had had prior KS therapy, so mainly those chemotherapies, immunomodulatory agents that I mentioned. Then in the second phase we enrolled up to 15 participants who had had prior KS therapy and 10 participants who actually had no prior systemic KS therapy. So could you use abemaciclib up front.

So we’ve enrolled 34 participants in this phase overall, 31 who have been evaluable for their KS. Our response rate so far has been 84%.

What were the findings?

The 34 participants with KS, 25 of whom have HIV, we found that among all participants the response rate for KS per the ACTG AIDS Clinical Trial Group criteria, which is a standard trial method for KS assessment, was 84%. Among those who had had prior systemic KS therapy the response rate was 81% and in those who had had no prior KS therapy, so in a person with HIV that just had ART for their KS HIV treatment, the response rate was actually 90%, so nine out of ten participants responded. So we’re very excited about those results.

Interestingly, we’ve also found that this therapy is actually T-cell sparing. So in a disease that’s driven by T-cell depletion, again T-cell dysregulation, this is a drug that actually doesn’t affect your CD4 T-cells. So that has been quite interesting to find as well.

What are the clinical implications of these findings?

We’re hoping that, given the excellent response rates, that this provides an option for participants in the future who have KS, both with and without HIV. It’s often a very stigmatising condition, especially in its association with HIV. We know that people with HIV at any CD4 T-cell count can develop KS and so this certainly provides an additional option, again, to avoid T-cell depleting therapies.

In terms of implications, we’re hoping that as we validate these findings with additional patients, participants in our advanced-stage cohort at our centre, we’ll hope that one day this will get incorporated into clinical guidelines for Kaposi sarcoma.

Is there anything else you would like to add?

It’s more that diseases like the ones we treat, Kaposi sarcoma is one that was identified very early in the HIV epidemic. So this is back in the mid to late ‘80s, early ‘90s, and young men were dying of this condition. Now it is much rarer because there are advances in HIV but it continues to be a cancer, again, that’s very stigmatising, is somewhat left behind with many advances and there have been few people driving these innovations. So I am very humbled to be one member of the team that has been really trying to promote understanding of KS and KSHV pathogenesis.