TRANSCRIPT

Dr. Ghassan Abou Alfa:  Hello, everybody. Welcome to ASCO. This is a little bit different this year. This is Ghassan Abou Alfa from Memorial Sloan Kettering Cancer Center in New York City. We're all at ASCO, and we're far away. We're close to each other at this important meeting.

I'm quite excited about ASCO this year because lots going on in regard to hepatocellular carcinoma. If I were to really divide it into three pieces, I would like to discuss...

Number one is the combination therapy. If you recall, this is a story that has been going on since ESMO Asia in December 2019. Number two is I would like to talk about the TKIs, and I would like to take them a little bit from a new perspective or a perspective that we discussed here and there about the etiology and the potential benefits.

Third, the combination of local and systemic therapy, something that also is not novel to us.

I start by the most important. There's quite a bit of information that came into that ASCO in regard to the combination therapy. Of course, we'll start with atezolizumab + bevacizumab. Nice piece of work that, in disclosure I was involved in, which looked into the competitor of the atezo + bev to the other lines of therapy part of two other clinical trials.

One of them is the lenvatinib or the REFLECT study. The number two is the CheckMate 459, looking at the nivolumab. Understandably, all three studies where they were compared to sorafenib competitor arm.

Using certain statistical tools that are rather pretty robust and would allow us to have a, what we call, network meta-analyses, we have found admittedly and not surprisingly that atezolizumab + bevacizumab performed quite better than the single-agent lenvatinib, than the single-agent nivolumab, which remember 459 was negative.

Two important components to note on that study -- number one is the tolerability of the "atezo-bev" compared to the different arms as well as in regard to, specifically, the sorafenib, which again is rather reassuring.

The other one, which not again comes as a surprise, but rather the pretty evident response capability of single-agent lenvatinib. We know very well that superiority of the atezolizumab-bevacizumab compared to the NIVO single-agent, and of course, compared to sorafenib, which was the IMbrave150 study to begin with was close between 90 to 85 percent, but it was only about 60 percent when it came to lenvatinib, which tells us about the potential benefit from the lenvatinib as well, with regard to response.

Beside that, a very big story that we are very proud of, and again, in full disclosure, I'm the senior author on and I give a lot of credit for Dr. Kate Kelley who represented us on that study, AZ22, looking at the tremelimumab plus durvalumab in advanced HCC.

Most importantly, this is understandably still a limited study. It looked at different combinations of therapy. As we can see from the presentation, we looked at single-agent durvalumab, single-agent tremelimumab, tremelimumab plus durvalumab, at two different doses and frequencies.

The one that really fared the best is the tremelimumab 300 single dose plus durvalumab on a regular basis. This is what we ended up calling T300+D. With one single dose, literally one single dose of the tremelimumab 300 plus the durvalumab, patients did fare extremely well, so quite exciting information was presented.

Most key is extremely high tolerability compared to, if you want other combination of the same nature like for example, the ipi/nivo. Number two is a great response rate for the T300+D of 24 percent. This translated of course in a survival benefit that, within the limited context of that study, was close to 19 months for the T300+D.

I totally agree with our dear colleague, Dr. Tim Meyer and his discussion that ultimately, the ultimate answer will be coming from HIMALAYA study.

An important point, and this is where I was searching through the abstracts as well, to see where we can see more of those stories, I was and I remain fascinated by the nice work that we did in regard to pharmacodynamic biomarker analysis. 26 lymphocyte populations were analyzed in a quadratic discriminant.

We found that a certain lymphocyte population that's predominantly composed of the CD3/CD8 and T67+ CT cell. Looking at it from two canons, the one that fares the best was the T300+D. Interestingly, we have seen that these absolute counts of the CD3/CD8 T67 were the highest among the patients with CR/PR among the different groups being the T300+D, or the single agents, or T75 single agent.

Nonetheless, a very important component which if you hold off for a second and bringing it back again, in regard to our next part of the story.