Phillip Koo:

All right, so now we're going to move on and stay in the advanced space and talk about this study called AMPLITUDE, which really had a lot of exciting conversation and buzz at ASCO. So, tell us about AMPLITUDE.

Zachary Klaassen: 

Yeah, so AMPLITUDE was another one of these big phase three trials where they took, again, with metastatic hormone-sensitive prostate cancer patients, and they took patients in this disease space, and they randomized them to a PARP inhibitor plus ADT, versus sort of standard of care plus ADT.

And the way…I just want to back up a little bit and talk a little bit about PARPs. So, PARPs are another oral medication. They've been approved in the mCRPC [metastatic castration resistant prostate cancer] state. So, this is the more advanced state than mHSPC. So, the combination of niraparib plus abiraterone plus ADT versus ADT plus abiraterone which was what was looked at in this trial. And so niraparib plus ADT already is being used in mCRPC. Now they're looking at they can move that combination up into the metastatic hormone-sensitive setting.

Now the difference with PARP inhibitors is that this opens another box of having tumor sequencing. So, there's different mutations that can happen, either in your blood, this is called germline, this is what you're born with, versus what's in the tumor, which is called somatic. So, to get into this trial, you had to have a certain [medication] called HRR mutations. And so, this is an entrance requirement. And so not everybody has these mutations, but this is what they looked at in this specific trial.

And so, what they found was… And PARPs go back a long ways in ovarian and pancreatic cancer, it's come into prostate in the last probably five to seven years or so. And we know that they work very well in these really advanced patients.

So, the AMPLITUDE study looked at this combination and to see if there was a benefit of adding the niraparib plus abiraterone plus ADT in an earlier setting. They found that there was a 48% reduction in radiographic progression in the triplet combination, as we'll say, versus the control arm, abiraterone plus ADT in the patients that have a BRCA, which is a common mutation, BRCA mutation.  Or, in the patients that had all of these other mutations, about 12 of them, there's a 38% reduction. So, it's kind of a long-winded way to say that this treatment, this PARP inhibitor, which breaks double-stranded DNA in the tumor, works very well for these patients if you have one of these 12.

Specifically, if you have this BRCA mutation compared to just abiraterone versus ADT. So, what we're seeing here, and this is not uncommon, we start with testing these in the very advanced state. If they work, we try to move them up so that more people may benefit from them. And certainly, AMPLITUDE had a lot of buzz because of that. So, we're seeing this combination of niraparib and abiraterone moving up potentially in this disease space.

Phillip Koo: 

You know, that's great. And I agree. I think this is sort of the promise of precision medicine. And for the listeners out there, we have very specific webinars at where we talk about genetic testing. We talk about germline testing. We talk about somatic testing. And this is exactly how we see that be put into action.

So for those, you know, have these conversations with your physicians if you have advanced disease and make sure you had the testing done, because that could help inform and get you into some of these different pathways that might have better improved effects compared to some of the other options that might be out there. So, this is really, really exciting.