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Adjuvant and Neoadjuvant Therapies with Dr. Mruthyunjaya and Dr. Funchain | The Eye Believe Podcast · The Eye Believe Podcast

0:03
hey omies welcome back to the Eye Believe Podcast
0:06
today we have two guests who are here to highlight
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just what's new in the treatments for ocular melanoma
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what you should know going into treatment
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if you're a new patient and we have two guests
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Doctor Funchain
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a uveal melanoma medical oncologist at Stanford
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and Doctor Prithvi Mruthyunjaya
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who you guys have seen lots of
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lots of things from him
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we are so grateful to him coming back again
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and bringing Doctor Funchain along for the ride
0:29
and he is from the Byers Eye Institute at Stanford
0:32
so we're gonna be chatting about neoadjuvant
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and adjuvant therapies in uveal melanoma
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don't worry we're gonna break these down for you
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in case you don't know what those words mean
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so just to start Doctor M
0:43
can you just tell us what is a neoadjuvant therapy
0:45
thanks Danet thanks for having us on board today
0:48
and talking about this very new
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exciting
0:51
but probably a foreign concept for many of our viewers
0:55
so by definition neo adjuvant therapy
0:59
is a treatment that's given as the first step
1:03
to try to shrink a tumor within the body
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in advance of a more defining therapy
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that would follow such as laser or radiation or more
1:16
more likely surgery
1:18
so the concept is that you have a tumor in the eye
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say ocular menoma um
1:24
if you could give that patient
1:26
either a systemic therapy
1:28
like chemotherapy or direct therapy
1:31
right to the eye for example
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and that causes that tumor to shrink
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the amount of secondary treatment that's required
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say the extent of surgery or the type of radiation
1:43
or the amount of radiation would potentially be less
1:47
but the other advantage is that if in fact
1:50
that tumor is shrinking
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with this predefinitive surgery approach
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then there may be a role that
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that neoadjuvant medication
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might be playing a role in the rest of the body
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as well and that might get into a way that by response
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or showing response
2:09
it may actually have a longer term benefit
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than just making that initial
2:15
eye related therapy more successful
2:18
or easier to uh
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to manage so
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neoadjuvant means treatment before definitive surgery
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or radiation usually with some form of
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of a specialized chemotherapy
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okay well
2:31
and you kind of alluded right into the adjuvant therapy
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as you kind of hinted at
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what we could use neoadjuvant for later right
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if it is successful in shrinking a primary tumor
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then we could get into the use of it adjuvantly
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so Doctor Funchain
2:44
do you want to tell us a little more about an adjuvant
2:46
therapy what does that mean
2:48
yeah so an adjuvant
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you can think of an adjuvant as a helper right
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so if you have surgery or radiation
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that's what we call sort of the definitive therapy
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that's the thing that's supposed to take everything out
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but what we know is that
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there's not a perfect guarantee that everything is out
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and that is usually because there is some kind of
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there's melanoma sometimes in the eye
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less commonly but that there's melanoma somewhere else
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like in the liver right
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and that would show up months to years later
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and the whole idea for adjuvant is that
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you take a therapy
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typically it's what we call a systemic therapy
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so a therapy that goes all through the body
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and then what that's gonna do is try to clean up any
3:31
any cells that have wandered somewhere else
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wandered off to the liver or lung or somewhere
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and so we actually have used adjuvant therapy
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in a lot of cancers
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I think people most commonly think about
3:42
people getting chemotherapy after breast cancer
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so you can have the surgery
3:45
and even radiation for breast cancer
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but you for some people when the risk is high enough
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you follow it up with chemotherapy so adjuvant
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we haven't really used for uveal melanoma
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but we're starting to think about
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drugs that might make sense in that place
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okay so we're mostly talking I'm assuming you know
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you guys in our audience
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you guys have probably had treatment for your uveal
4:11
melanoma so let's just kind of
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to make sure that we don't have anybody
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tuning out and go like
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oh this isn't for me why is this important
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even if you've already been treated say five
4:19
10 years ago months ago
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why is this important for patients to pay attention to
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now so um
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what we found I think one of the
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the really interesting things about both neo
4:29
adjuvant and adjuvant therapy is
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if we find signal in either of these areas
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then what we've done is said look
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this drug works in a smaller setting
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right in
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in either it's just melanoma
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just in the eye or just a few cells somewhere else
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if we find that there's signal
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so if these trials come up to be positive
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which means there's there's an effect
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like a good effect a positive effect
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if there is an effect then
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that starts telling us that these drugs
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might be useful in any setting right
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might be useful
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should the cancer come back in the future
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maybe
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these drugs are something we should think a lot harder
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about or combine with other things
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so seeing a signal in these settings is
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and because they're you know
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way fewer treatments than we'd like to have
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in all settings
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any signal anywhere we will take across the spectrum to
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to echo that it's a really great way to think of it
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that even if you've already been treated
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it doesn't mean that
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that information couldn't be beneficial to you
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if not today into the future
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and a couple of things that
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you know kind of come into play
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everyone always wants to know about
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you know
5:40
are there clinical trials or options that are available
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and if
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we didn't have this information available to us in the
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either the neoadjuvant or even adjuvant setting
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then it's hard for companies that are like
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making these blockbuster drugs
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to even think about its utility for us
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so
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the more options that our patients are involved with
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in earlier clinical trials
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really makes the entire ecosystem
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of what's gonna be available for our patients
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much broader and much richer
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and um
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you know
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the other area that many people may have heard of
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neoadjuvant
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and adjuvant treatment is in skin melanoma
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so we tell everybody
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uveal and skin are two different distant cousins
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but we do take a lot of
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information and knowledge from Doctor Funchain's
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colleagues and herself
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who have done a lot of work with metastatic
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cutaneous melanoma so skin melanomas that have spread
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and there is some you know
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very compelling data using say
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checkpoint inhibitors which we tend
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you know not to
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use as like the absolute perfect way
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and Pauline can correct me
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to treat you know
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metastatic uveal melanomas
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they have a role in it but man
6:59
in skin melanoma it really seems to make a difference
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that if you treat someone up front
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with this powerful immunotherapy
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and then take them to surgery
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and then follow them up with
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that same medicine afterwards
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like
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it can make a really big difference in their survival
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Pauline would you
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is that even close to true or
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well that's totally true
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so we've essentially taken
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because as a melanoma oncologist
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you treat skin you treat mucosal
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you treat uveal melanoma
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we have wholesale taken anything that works in skin
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and moved it along to to mucosal and uveal
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because while there are huge differences in biology
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between all of these melanomas at
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at the base they are all melanoma right
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so there are some commonalities
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and the I think
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we haven't found that things in cutaneous melanoma
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so this is the hard part right
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as a patient when you read about melanoma
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you'll often read about things that are
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that pertain to skin melanoma
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and you really hope that it applies to you
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unfortunately they don't apply across the board
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however
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I think we have learned a lot
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there are some efficacy signals in the other melanomas
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and I think what we need to find in the non
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skin melanomas in uveal and mucosal
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is just tweaking what we've done in skin
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and tweaking it the right way
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so we haven't found the magic tweaks
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but we found some decent tweaks and
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and I think we'll find more
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but it's a great place to start because honestly
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if we look at 10 years ago
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we didn't have a single FDA approved drug
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and now we do and not only
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and just as you said
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now that we've had that FDA approved drug
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for uveal melanoma
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that has been a watershed for companies
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to get interested in this space
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and that you know I
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I just so I just gave a talk on uveal melanoma and
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and the joke was like a couple of years ago
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this was always the shortest talk
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if you were giving the uveal melanoma talk
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and I I had so much in that talk
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I could not fit it all in
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that's the the magic of having just one FDA approval
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it just breaks open the science behind
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trying to get this cancer off our radar
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Danet another area that we need to also touch
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when we talk about neoadjuvant therapies
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so to be clear there are no
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approved neoadjuvant therapies
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for our patients with uveal melanoma today
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20 in March of 2025
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however if that neoadjuvant strategy bears fruit
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there could be a couple of
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you know really good things that can happen
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first as we all know
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there are side effects from the treatments that we have
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for treating ocular melanoma
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though they are great radiation therapy
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surgery for eye removal very
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very high rates of local tumor control
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we can control the cancer in the eye
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now imagine if you could treat a patient with radiation
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that you know
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could have side effects and Danet
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you've talked about radiation
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retinopathy
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and other side effects on your podcast before
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we know that there are still no
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like approved therapies for that
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imagine if you could take a tumor treat
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treat the patient before radiation with chemotherapy
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that shrinks that tumor by
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let's say half right
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it makes intuitive sense that maybe
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you'd have to use much less radiation
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to treat that same tumor with the same great outcome
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in terms of the ability to control the tumor
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within the eye but if you're using say
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let's just say 50% less radiation
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you might you might guess
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that some of those side effects will be less
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I'm not saying it'll be 50% less
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but maybe it is we don't quite know that
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or a patient who has a very large tumor
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that we know
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that enucleation would be the recommended treatment
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if there's an effective neoadjuvant treatment
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what if we took that very large tumor
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and made it small enough that
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then radiation could be used
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yes it's still a lot of radiation
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and there are side effects
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but we might be able to save some eyes in that process
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so there's a local benefit if
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if we have good neoadjuvant strategies
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and then the secondary effect is
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what Pauline's talking about
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is that maybe then
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those cells that have potentially left the eye
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and are floating around
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that we can't detect on an MRI or a cat scan
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maybe those get attacked also by the same medicine
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so we're looking at the eye
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but the medicine is surveying the whole body
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and maybe that one rogue cell
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that one rogue cell
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gets eliminated in the process of prepping the eye for
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you know definitive surgery with maybe less side effect
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now this is all very theoretical
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but wow the eye is such an important organ right
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it's so much more complicated than saying
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I'm taking a piece of my liver out
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and it'll regenerate that doesn't happen in the eye
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so you know
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with these brain functioning tissues like the eye
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any way that we could you know
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reduce side effect I think that's a plus
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yeah no
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it's definitely a plus I mean
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speaking of someone who ended up with
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enough radiation damage to her eye
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that I had to have it removed eventually
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like not because the tumor wasn't
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you know treated adequately
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it was just because the radiation damage was so bad
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that the eye was no longer considered
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healthy to keep in my in my body
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and I I've heard of people
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you know
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currently who are on these neoadjuvant trials at least
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so that was what I was gonna ask you
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Doctor M is you know
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I don't we don't have anything approved in the space
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you're right but do we have anything that is currently
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actively recruiting for you know
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clinical trials in the neoadjuvant setting
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and if so what are those
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yeah so um
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we've been really fortunate
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when Doctor Funchain joined us here at Stanford
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that she was very aggressive in
12:56
in bringing the latest clinical trials that really have
13:00
you know sound biological functioning so um
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we are working with a uh
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company called Ideaya who have uh
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brought forth a neo adjuvant study in uveal melanoma
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using a drug called Darovasertib
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or Daro for short
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this is a drug that blocks a particular
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protein that we find active in uveal melanoma called
13:25
it's a protein kinase C inhibitor
13:27
really smart science that has to put this together
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and it's been used
13:31
in patients that have metastatic melanoma
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and then they found incidentally
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some patients when they examined their eyes
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their ocular melanoma got smaller
13:42
so um
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they have set up a uh
13:45
clinical trial now that's in
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in the phase 2 a part of the approval uh cycle
13:51
so um
13:51
they have two arms to this study
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one is to give this medication prior to uh
13:57
patients who might be undergoing enucleation
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to see if
14:01
a percentage of those wouldn't need enucleation
14:05
and could be treated with radiation
14:06
and try to save their eye up front
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and then a second arm um
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which I think is very compelling
14:13
is patients that are getting radiation treatment
14:16
uh as planned therapy
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they receive this neo adjuvant therapy up front
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and then to see if that tumor shrinks
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so that the radiation dosing is decreased
14:27
um Doctor Funchains
14:28
the uh uh
14:29
principal investigator of the trial here at Stanford
14:32
and I think she probably can tell you
14:33
even a little bit more about it
14:35
yeah that'd be awesome
14:36
Doctor Funchain do you want to tell us a little more
14:38
yeah I think a couple of things about the trial
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so there
14:41
were some preliminary results that were very promising
14:46
so one of the earliest patients
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was somebody who would have needed their eye taken out
14:52
to get an enucleation
14:53
and they were able to have such shrinkage with this
14:56
neoadjuvant treatment
14:58
that they were able to save their eye and do radiation
15:01
right we don't know all of the
15:04
the consequences of this but that is
15:06
you know we know that
15:07
that being able to save an eye when it's possible
15:10
really means a lot to patients right
15:12
so this is a really meaningful response
15:15
and we have seen
15:16
since this trial has gone on from phase 1 to phase 2
15:19
and has a much larger number of people who are treated
15:22
that person is by far not the only one
15:25
there are some very promising results about
15:28
in terms of um
15:29
patients being able to save their eyes
15:33
and then
15:33
others who have had their radiation field reduced
15:36
now does it work for everyone so far
15:38
you know it's not a perfect magic bullet
15:40
but it's really promising
15:42
and it the drug itself is decently tolerable
15:46
I think we've definitely seen combinations
15:48
that have more toxicity than this
15:51
so right now we are seeing some good results
15:55
it's this trial is still ongoing and
15:59
but there is movement to try to make this bigger
16:02
and potentially go for an FDA approval
16:04
which I think is very reasonable
16:06
given what we've seen so far
16:08
Danet this is also paradigm shifting for us right
16:11
because if you if you think about it
16:14
you know the ocular oncologist sees the patient
16:17
we decide on the treatment
16:19
we might do a biopsy we might determine
16:22
you know whether someone is high risk or low risk
16:24
and then they meet Doctor Funchain after that right
16:27
so surgery is done you know
16:29
eye is removed radiation is
16:31
is produced and then
16:32
you know
16:33
she's in charge of making sure that the screening
16:35
is done properly
16:37
early tumors are caught and treatment is initiated
16:40
this is an excellent opportunity for the
16:43
the all members of the team
16:45
the medical oncologist the radiation oncologist
16:48
and the ocular oncologist to meet up front right
16:52
so we're taking a team approach to um
16:55
addressing a small thing in the eye
16:57
but more importantly like
16:59
you know preserving the body
17:01
um and so
17:01
I think that's a real great intersection that
17:04
I think we're all enjoying
17:06
um that we get to now
17:08
hear some of the vast experience
17:10
that our medical oncologists have had
17:12
with neoadjuvant therapy
17:14
that ocular oncology really hasn't
17:16
with the exception of
17:17
when we treat our babies with retinoblastoma
17:20
which is a eye tumor that occurs in children
17:23
we've been giving chemotherapy to them up front
17:25
in a neoadjuvant setting
17:27
you know for now several decades
17:30
I think the challenge in uveal melanoma
17:32
has been that we haven't had um the
17:35
the right drugs we haven't had the right approach
17:38
and we haven't had enough interest
17:40
it's like perfect timing like
17:42
we have a drug that seems promising
17:45
with a team that's now bringing it together
17:48
and then now
17:48
this community of medical and ocular oncologists
17:52
and radiation oncologists that are trying to um
17:55
move this forward I'll just add one quick thing about
17:58
Dr. Mruthyunjaya makes a fantastic point
18:01
in medical oncology
18:04
not just not just
18:05
you know uveal melanoma
18:07
not just cutaneous melanoma
18:09
um but in other cancers
18:10
we have used neo adjuvant approaches
18:13
so doing treatment before the definitive surgery
18:16
or radiation and in many cases
18:19
what we find is that if you start that early
18:22
when there's less cancer to deal with right
18:25
that's like sort of
18:25
the earliest time that you can put something systemic
18:28
something that goes all through the body upfront
18:30
when there's less disease
18:32
you can actually
18:33
not just improve what's going on in the eye
18:36
and treatments for the eye
18:37
but you can then improve overall survival
18:40
so you know
18:41
all the
18:42
potentially getting rid of the cells outside of the eye
18:45
and so there in many cases
18:47
you're doing two things
18:49
and we kind of mentioned this before
18:50
but you know
18:51
I just want to emphasize that this is a possibility
18:53
we haven't seen the data yet from this trial
18:56
but we're really hopeful that when you start early
18:59
with fewer cells you can
19:01
it's easier to knock everything out
19:03
if there's stuff outside of the eye
19:05
yeah I mean
19:06
I feel like that theory makes sense
19:08
when you think about the idea that okay
19:11
the primary eye is the source of the cancer
19:13
or the primary tumor in the eye
19:15
that's the original source
19:16
but then there's these potential micrometastatic cells
19:19
that at some point
19:21
have gotten out before the eye
19:23
you know the eye tumor itself is controlled
19:25
and so I love the idea and I love the science of it
19:28
I love the hope that is behind that idea
19:31
and just
19:31
I think that even just patients leaning into that as
19:34
as they participate in these trials
19:35
like leaning into that mindset of like well
19:37
as long as you know I have a chance
19:39
like this sounds like a good chance
19:41
and I can't imagine that's not gonna be unhelpful
19:43
even just from a mental health perspective
19:45
like for these patients to you know
19:47
come into a diagnosis and learn you know
19:49
not only do they not have to necessarily
19:52
say goodbye to their eye immediately
19:53
they have a chance to keep it and it
19:55
it might actually
19:56
give the rest of their body a really good shot too
19:59
so I really like that
20:00
and I think that you guys both like
20:02
bring really good attention to kind of
20:04
the nuance of the space right
20:06
which is that there isn't all of the data
20:07
we don't have all of the answers yet
20:09
but we are still evaluating it
20:12
the trials are still happening and that's a good thing
20:16
so are the trials that are happening then
20:18
in the adjuvant treatment space
20:19
are they are they always related to neoadjuvant or
20:23
you know
20:23
cause I know Ideaya is kind of a I've interviewed
20:26
Darrin Beaupre from Ideaya before
20:29
and he talked a little about
20:31
just kind of
20:31
the unique way that they've structured the arm
20:33
of their trials and I know that they're going about
20:35
doing that a little bit differently
20:37
than most pharmaceutical companies
20:38
and drug companies do where they've got
20:41
you know the neoadjuvant arm
20:42
the potential adjuvant arm
20:43
and then the metastatic arm
20:46
and kind of multiple branches within that
20:48
within each of those so
20:50
that's kind of a newer way that we're seeing uveal
20:52
melanoma treated in the trial space
20:54
do we have any other you know
20:55
adjuvant trial treatments that are happening
20:57
that you know of right now
20:58
Doctor Funchain that's a great question
21:00
so we have talked about before that the one
21:05
FDA approval for Tebentatusp
21:07
or KIMMTRAK
21:07
has really opened up the minds of pharmaceuticals
21:11
and I actually love Ideaya's approach
21:13
they've been very molecularly smart about
21:17
how they're thinking about their strategies
21:19
but I will point out right now for this study
21:22
it's neoadjuvant and then
21:26
you know you get your definitive eye treatment
21:28
so surgery or radiation
21:29
and then there's the option to continue adjuvantly
21:33
however
21:34
there isn't a trial to continue adjuvantly by itself
21:39
yeah by itself
21:40
so if you've already had the surgery
21:42
and you haven't had the neoadjuvant
21:43
and haven't been in the study
21:44
there isn't the option
21:45
and in that sense we are very happy that they are
21:47
trying to go after FDA approval
21:49
as soon as possible cause
21:50
we want to get this to as many patients as possible
21:52
right it shouldn't be just
21:54
you live near a trial center
21:56
or you have the means to travel to a trial center
21:58
so in that way we are
22:01
we are with the company
22:02
to just get this out to as many people as possible
22:05
right so
22:06
in the adjuvant setting there have been very few trials
22:10
I will say again cause
22:11
we didn't
22:12
totally have a sense of what drugs might work
22:16
but there was a really impressive adjuvant trial
22:19
that was presented at our oncology meeting
22:22
and that trial was looking at adjuvant um
22:25
Yervoy Opdivo or Ipilimumab
22:27
nivolumab and that's checkpoint inhibition
22:30
that is the traditional immunotherapy that
22:32
if you look up skin melanoma
22:33
you're going to find this
22:35
this regimen and they did a slightly different
22:39
slightly different dosing than what we use in skin
22:41
so the um
22:43
Yervoy part of it
22:44
which tends to be the more toxic part of it
22:46
was a lower dose and less frequent
22:49
and with the same Opdivo but this combination
22:51
immunotherapy was given after having either
22:55
you know surgery or radiation
22:58
and they actually um
23:00
showed in that study that there was about half the risk
23:05
of recurrence at the three year mark
23:08
which is really impressive
23:10
now this is a small study
23:12
whenever you do a small study
23:14
we all know in the cancer world
23:16
that when you repeat it with a larger study
23:17
it doesn't turn out as you think
23:19
there are some things that are wildly positive
23:22
when you do the small study
23:23
and when you go to the big study
23:24
it totally washes out however
23:26
this is super promising
23:28
there's a big debate and continues to be a big debate
23:30
this is off trial use it is not FDA approved
23:34
do you use it or don't you use it
23:37
and I will say that's very
23:38
very provider specific
23:40
I can also say that that trial has clearly
23:44
because it the results were very promising
23:48
that will expand to a phase 3 trial
23:50
but it is under negotiations
23:52
it is partially government sponsored trial
23:55
you know
23:56
with the uncertainty that is coming out of Washington
23:59
nowadays the funding for government sponsored trials
24:03
is a little bit uncertain
24:04
so we don't know but so far
24:07
the signals are that this
24:09
this trial will continue and we hope it will
24:12
well I think that's really promising
24:14
so if anybody wanted to look that up
24:16
would they be able to look up like
24:17
just some kind of generic terms
24:19
like ipi nivo uveal melanoma adjuvant trial
24:22
or adjuvant exactly yep okay
24:23
yep yep
24:25
alright
24:25
so that would be a good thing to search for sure
24:27
and then was there anything else like
24:28
cause I I know when I first was diagnosed
24:30
I was part of like the Sutent (sunitinib) and the VPA trial yeah
24:34
that that was yeah
24:34
mostly headed out of Jefferson yeah
24:37
I still ended up with metastatic disease
24:39
and it's like
24:40
half the people that were on the trial with me did like
24:42
so again small study
24:43
like what's the data like how does
24:45
how does it help how does it not
24:46
um yeah
24:48
anyway yeah
24:48
that Sutent study was very popular
24:50
there was actually a crizotinib study
24:52
or XALKORI study
24:54
that was very small and very popular
24:56
but very I mean
24:57
really no signal so
25:01
so we those have not gone on um
25:03
but those those were the
25:05
those were the studies
25:05
we were desperately trying to get people on
25:07
because there were very few spots
25:09
and very few places that were
25:11
that had them open
25:12
and really there had been nothing since
25:15
um until this yervoy opdivo study
25:19
and so now we're waiting for it to reopen
25:22
you know looking at it also from the patient side
25:25
something to keep in mind is even if these studies were
25:29
um not positive enough to move forward
25:33
I think that as a community
25:34
we've learned a lot from them
25:36
you know so in
25:37
in a setting where we don't have options
25:39
you know some of the things that have come up is that
25:41
how do you design clinical trials
25:44
for this very unique disease right
25:47
instead of taking all comers
25:49
do we then use genetic stratification
25:52
so that we put patients at highest risk
25:54
into the trials
25:55
rather than not including patients that
25:58
you know are at very low risk
26:00
you know that might muddy the um
26:03
the uh outcomes
26:04
um how
26:05
what do we use as a control population
26:07
how do we design dosing
26:10
as much as that sounds so minute and so incremental
26:14
it's so important right
26:15
because when you have a rare disease
26:18
what you want is a home run
26:20
with the next treatment that comes out
26:22
but sometimes you gotta take some
26:24
you know some cracks at
26:25
at practice you know
26:27
hitting the ball just right and
26:29
you know sometimes you get really lucky up front
26:31
but sometimes it's it's incremental
26:33
but I think the fact and Dr. Funchain alluded to this
26:37
that we have you know
26:38
this interest now from um
26:40
the biopharma companies
26:42
and they understand that there's
26:43
something unique about these tumors
26:46
that are that are potentially addressable
26:49
in ways that other tumors aren't
26:51
and for them
26:52
if they can get a drug across the finish line
26:55
as we say meaning
26:56
approved and available to patients in one disease
26:59
then they'll try to look at it in other diseases
27:02
as well so um there
27:04
there is a lot of interest
27:05
so I think that that is something that we should all be
27:08
um you know
27:09
encouraging you know
27:10
people to be involved
27:11
in trials and for better trials to come forward and
27:14
and I think there there are some interesting um
27:17
you know drug candidates and molecules
27:19
and trials that are coming forward from companies
27:22
and as Pauline said go back a decade
27:25
there was like you know
27:26
there were crickets like it was silent
27:29
um
27:29
people trying to do their best with what was available
27:31
now we have you know
27:32
uveal melanoma specific targets and drugs that um
27:37
that people are trying to move forward
27:40
um it's a very different game
27:42
I've got to expand that and emphasize some points that
27:44
Doctor Mruthyunjaya said
27:45
he's so right on the money
27:46
because if you think about the Sutent trial
27:49
and you think about the XALKORI trial
27:52
these were the sort of
27:54
great grandparents of the Darovasertib now
27:58
right of the Ideaya trial now it
28:00
I mean they're all in the same family right
28:02
they are these molecularly targeted
28:05
you know small molecules
28:07
and those didn't quite work
28:09
and there were and
28:10
and not to say just because a trial is negative
28:13
doesn't mean there isn't a little bit of signal
28:15
we have seen that a lot but there's something in there
28:18
whether you are looking at the biologic samples
28:20
that come from those trials
28:21
because as anyone who's done a trial knows
28:23
they take a lot of blood and tissue from you
28:25
at the same time but
28:27
there are biologic
28:29
discoveries that we make from those samples
28:31
but also we we just again
28:33
it's the tweaks right
28:34
so this is a molecularly targeted small molecule
28:38
we tried the Sutent version
28:39
we tried the the XALKORI version
28:42
and actually
28:42
the XALKORI version along with Darovasertib
28:45
that actually is showing some promise in
28:48
in metastatic uveal melanoma
28:50
so actually that it was
28:52
it was going from Sutent to this combination
28:54
that actually LED us to just using Darovasertib alone
28:59
in the neoadjuvant and that's where we got the results
29:01
so it is they all build on each other
29:04
same with Yervoy Opdivo
29:05
so we've all done Yervoy Opdivo
29:08
in the metastatic setting
29:09
there were two different phase 2 trials
29:11
and we did a really large retrospective analysis
29:15
looking at the effects and again
29:18
well that technically the
29:20
the trials were technically negative
29:22
we definitely saw signal
29:24
there were definitely some people who benefited um
29:27
and some tumors that that shrank on these trials
29:30
and so
29:30
based on those trials that were technically negative
29:33
in the metastatic setting
29:35
we then moved it
29:37
and then tweaked it and tweak the dosing
29:38
and then put it in the adjuvant setting
29:40
and now
29:40
we're starting to see something that's a good effect
29:43
so I think that these are
29:45
these are the tweaks right
29:46
every trial you you tweak and get to something better
29:50
and now we have some really good results
29:52
from trials that were done
29:53
you know about 10 years ago
29:55
well I feel like this is a really good
29:57
way to illustrate that they're all related right and
30:00
and they're all related
30:01
in the sense that the treatments
30:03
you know
30:03
we've got metastatic treatments that are happening and
30:05
and most of the time
30:06
when you hear about clinical trials
30:08
it's for the metastatic treatments right
30:10
we've got the the bulk of the
30:12
you know
30:13
we do have far fewer clinical trials than other cancers
30:16
but the bulk of our trials live in the metastatic space
30:19
and then we have some of those that then kind of
30:22
by nature
30:23
or you know
30:24
or relation to other adjuvant trials
30:26
things like that the things that you talked about
30:28
we've got the
30:28
the adjuvant trials that have happened in the past
30:31
or that have contributed to what are we doing next
30:33
and why and just kind of
30:35
the creative use of these drugs in the space um
30:38
adjuvantly and then we have kind of the
30:40
I think the newest thing that we're hearing about
30:42
is the neoadjuvant of like
30:43
oh well let's
30:44
let's actually start before we treat the eye uh
30:47
and and I think that the
30:49
like what Dr. Mruthyunjaya
30:50
and both of you were saying is just
30:52
it's just so neat to see how
30:54
you know how you're
30:55
you're connecting all the pieces um
30:57
and connecting them far earlier
30:59
and kind of forcing the collaboration of all of these
31:02
these different areas of medicine
31:04
you know because we do have so many different doctors
31:06
you're just kind of bringing them together in a
31:08
a much more advanced proactive setting
31:11
I think is maybe a good way of thinking about it
31:14
if we could also like
31:15
you know look into the crystal ball
31:16
I think that this would also be a
31:18
a
31:19
yes we I
31:20
I think we should um
31:21
because I think that this may also pose a model for
31:26
what we'd call precision medicine
31:28
or very customized treatments for patients
31:32
so some of the work that we've been involved with
31:34
here at Stanford is looking at
31:36
signatures that individual tumors may possess
31:40
that we can detect on taking very uh
31:43
simple fluid samples from the eye
31:45
and we can see certain proteins that are elevated
31:49
or decreased in certain tumors
31:51
and each one could be a little bit different
31:53
I mean let's imagine a world where um
31:56
you know before treatment
31:57
you could define
31:59
what is actually active in a particular person's tumor
32:03
and with all of the techniques we have
32:05
with intraocular surgery
32:07
directly deliver that to the patient's eye right
32:11
so if you could customize
32:13
you know patient a has tumor type B
32:17
and that means only drug C would work
32:20
why would you give that patient drug d or
32:23
you know drug F
32:24
like that would that could probably fail
32:27
so I think that
32:28
one of the things that we're trying to work on here is
32:30
how can we
32:31
use some of this clinical trial data that we have
32:35
that's developing how can we
32:37
learn from that
32:38
with these other biomarkers that may be available
32:42
and then ultimately how can we come up with um
32:45
very defined treatments that could be very customizable
32:49
it's a it's a stretch
32:50
I it
32:51
it sounds like a stretch but maybe not so much
32:53
like there are other tumor types that that's been
32:56
that's been successful in
32:58
and I I
32:58
I feel like now just like with
33:00
you know people on Sutent has now led to us having
33:04
you know Darovasertib available
33:06
everything that we've learned from previous trials
33:09
might define where we can take those next uh
33:12
bold steps going forward so our
33:14
our team here at Stanford
33:15
has been very interested in trying to push this
33:18
and it really it takes a team
33:19
right between the medical and the ocular oncologist
33:22
our scientists and most importantly
33:24
our patients who have been so um
33:27
receptive to being parts of these studies
33:30
I think that's incredible
33:31
is there any other areas of like the
33:33
the research that you guys are doing at Stanford
33:35
that you're just particularly excited about
33:37
Doctor Funchain
33:39
oh yeah
33:39
uh yes
33:41
yes we do hahaha
33:43
we have actually
33:44
an open clinical trial that is worth talking about
33:47
so this is in the metastatic setting
33:50
it is an injected drug called RP 2
33:54
and what that
33:55
that does is it's injected into a liver tumor
33:58
or something that you can get to with a needle
34:00
and it also then has Opdivo
34:05
an immunotherapy and combines them
34:08
we have seen some preliminary
34:10
results of tumor shrinkage
34:12
in uveal melanoma
34:14
so not just the thing that was injected
34:16
but other lesions that aren't injected
34:18
will also decrease in size
34:21
the important thing to know about this trial is that
34:25
it does not allow
34:27
so for those of you are familiar with the trial space
34:29
there are a lot of check boxes that have to be checked
34:32
to get onto a trial
34:34
but one of the important check boxes to know
34:36
for this trial is that
34:38
a patient can only have seen one line of therapy
34:40
and cannot have had liver directed therapy
34:43
so if there's any liver and embolism or Y90
34:47
or any of those liver specific
34:49
or Delcath any of those therapies
34:52
then this trial doesn't apply
34:54
so this is one of those things where they're just again
34:57
they're trying to test early to see what they can find
35:01
I mean I think at some point if we see good data
35:04
this may expand
35:05
but right now that that's what the trial allows for
35:08
but we've seen some pretty good results up front
35:12
and a trial that is nearby in the Bay Area and in many
35:16
many places is the trial that we just talked about
35:20
which is the Darovasertib plus Crizotinib or XALKORI
35:24
both of these trials have a very similar efficacy
35:27
so they are able to shrink tumors um
35:30
by about 30%
35:31
so that's pretty good or about 30% of people have tumor
35:34
shrinkage so these are some promising studies
35:37
and I think again as we do this
35:39
then we'll be able to tweak
35:41
we'll understand what order these things should go in
35:43
but it's really promising
35:45
I think we're having a lot of breakthroughs
35:47
and that neoadjuvant adjuvant
35:49
and metastatic areas or settings all at the same time
35:53
which is pretty fun for us and hopefully
35:56
knock on wood you know
35:57
good for patients with uveal melanoma in general
36:00
so I did have a question
36:02
do we have any noise about yet in the use of Tebentafusp
36:07
Adjuvantly like saying that oh
36:09
we've got high risk patients
36:10
they have a class 2 you know
36:12
very high risk of spread uh
36:13
tumor and they are also HLA positive or HLA 0 2
36:18
0 1 positive
36:19
therefore we're gonna put them on Tebi once a month or
36:22
you know once every 6 weeks
36:23
like just like a
36:24
some kind of a different dosing of using Tebi
36:27
is that has
36:28
has that been noised about at all in
36:29
in meetings that you've been in
36:31
been to lately I think
36:32
I don't know if you've heard
36:33
if you've heard more recent stuff than I have
36:35
but there is noise and it
36:37
it hasn't come to being yet but
36:39
but we think that there might be something coming
36:42
you know in the future
36:44
yeah just
36:45
it all takes time like
36:46
and that's that's one of the hardest things
36:48
and I I do appreciate that you alluded to
36:50
you know just kind of the
36:51
the current political climate
36:52
and just what's going on in
36:54
in the government space that is affecting our research
36:57
um our researchers
36:58
our doctors facilities like Stanford
37:01
uh where they do heavy
37:02
you know amounts of research and um
37:05
other facilities like
37:05
we have so many fantastic doctors throughout the uveal
37:09
melanoma space and a lot of them are both doctors and
37:13
you know
37:13
they're seeing patients and they're researching
37:15
and I think Doctor Mruthyunjaya
37:16
Doctor Funchain you guys are both
37:18
both in that space and we really just appreciate
37:21
all of the work that you guys are doing
37:22
and just being honest and open
37:24
but also helping to bring and shed some light on
37:27
you know
37:27
the fact that there's so much more than cricket noise
37:31
that you know
37:31
existed 10 years ago
37:33
so I really appreciate you guys both being here
37:35
it's a pleasure thank you for the invitation
37:37
this has been great thank you so much
37:39
Danet those of you guys listening
37:41
Doctor M wants you to know
37:43
uh I want you to know that um
37:45
that there's a new
37:48
paradigm that's being tested now in clinical studies
37:53
that might allow for uh
37:55
patients to have benefits not only to their eye
37:58
but also to the rest of their body
38:00
most importantly the days are uh
38:03
not as early as we think
38:04
but the data has still to show us
38:08
but I think it's opening doors for our
38:10
patients going into the future
38:13
and I think we all need to be aware
38:15
that there will be opportunities
38:16
to be parts of these trials
38:19
and that we should all participate
38:20
and most importantly um
38:23
The Byers Eye Institute is uh hosting our 5 k uh
38:28
event again with A Cure In Sight on July 12th
38:31
it is the best one in the whole country
38:35
I mean so I'm
38:36
I'm just saying it's I haven't I'm not saying this
38:38
I've heard that it's the best one in the whole country
38:41
so um we uh strongly encourage um all of our patients
38:45
their families their friends to come and celebrate um
38:49
their survivorship journey and to help us um
38:52
uh raise uh
38:53
funds for this important research
38:55
that's happening across the country
38:57
uh here at Stanford
38:58
we uh share all of that back with A Cure In Sight
39:02
because we want uh
39:03
this to multiply um
39:05
across the country and around the world
39:06
so see you on July 12
39:10
I love it well yes
39:11
I have been to Doctor Mruthyunjaya's
39:13
5 k at the Byers Eye Institute
39:15
and Rose Angel and just their whole team is
39:18
they are a team of superheroes
39:20
putting on these 5 K's and helping A Cure In Sight
39:22
those of us in our side of the team
39:24
so thank you for that note and also happy
39:27
happy birthday
39:28
gonna be a little belated for anybody listening
39:29
but happy birthday
39:30
yesterday was Doctor M's birthday so we're so grateful
39:34
that you are here um
39:36
celebrating a little bit this month with us
39:37
and talking and just giving us some hope
39:39
so thank you for that Doctor Funchain
39:41
is there anything that you feel like
39:42
you would like our listeners to know
39:43
those of them listening right now
39:45
I I'm gonna dovetail on
39:47
on Doctor Mruthyunjaya's comment
39:49
so I think A Cura In Sight is a perfect example
39:52
of how much progress we make when we work together
39:56
I have to say that some of the uveal
39:59
melanoma patient advocates are some of the strongest
40:02
folks that I know they have really
40:06
not just weathered what they have had to weather
40:08
but have really come out to support
40:12
the rest of the community
40:14
I think I I have had more patients in uveal
40:16
a melanoma than any other melanoma talk about um
40:19
patient forums online and how they support one another
40:22
and you know
40:23
believe me being online is tough I understand haha
40:27
you hear all of it
40:28
and often you hear the wide disparities
40:30
the really good stories and the really bad stories
40:32
but I I think that this is
40:35
I think that things like this things like a run
40:37
things like being a part of this podcast
40:39
being part of those forums
40:40
I mean I think everyone supports one another
40:42
and when it comes to something that is a little bit
40:44
on the rare side
40:46
a little bit less known by all the doctors
40:48
except for you know
40:49
and the specialists I think
40:51
it's really important that everyone comes together
40:54
to make these changes make noise um
40:57
help support our funding for
40:59
for uveal melanoma and generally speaking
41:03
cancer research you know I
41:05
I think it's been such a pleasure
41:06
to be part of a multidisciplinary field
41:09
that includes not just our ocular oncologist
41:12
like Doctor M
41:12
but our radiation oncologist and our patient advocates
41:15
I think we all work together
41:16
so
41:16
it's been such a pleasure to be part of this community
41:20
thank you guys
41:21
thank you both so much and let's just
41:22
I think let's just end with the idea that you guys
41:24
let's look out for each other
41:25
let's look out for each other
41:27
I mean
41:27
we've got our doctors looking out for our patients
41:29
and for each other and then as patients
41:31
let's look out for each other
41:32
so if you find somebody who's newly diagnosed
41:35
tell them about this podcast
41:36
um
41:36
make sure that they know that they can stay up to date
41:39
and that there are hopeful things on the horizon
41:41
there could be you know
41:42
kind of newer things that could be happening
41:44
that they should know about
41:45
especially if they're newer to the treatment center um
41:48
or to the treatment space
41:49
um and let's just
41:50
you know I hate to use the
41:52
the eye puns but like
41:53
let's literally look out for each other
41:54
in all the ways that we can
41:56
alright well
41:56
I think we will go ahead
41:57
and say goodbye to our listeners
41:59
um thank you guys for tuning in
42:01
if you guys have not
42:02
make sure to subscribe on our YouTube channel
42:04
um help us get over 1,000 subscribers
42:06
and then we can start monetizing our YouTube channel
42:08
and please please
42:09
please come to those local events that we are hosting
42:12
like the 5K in uh Palo Alto with Dr. Mruthyunjaya
42:15
and the Byers Eye Stanford team
42:17
we're so grateful for them
42:18
we've got couple of other really good
42:20
highly attended 5 Ks happening
42:22
I think we've got a couple in Seattle or let's see
42:25
Doctor Dalvin in the Mayo Clinic in Minnesota
42:28
we've got Doctor Stacey in Seattle
42:31
Doctor Moser out here in Scottsdale
42:33
so there are a few key locations
42:35
I do have to hand it to Doctor Mruthyunjaya though
42:37
they are the highest attended 5 k
42:39
ever in the history of uveal melanoma
42:42
and they have fundraised the most
42:44
for uveal melanoma medical research
42:46
so if you guys want to
42:48
you know get in on the competition
42:50
then tell your doctors let's get involved
42:52
and let's just all look out for each other
42:54
we'll see you guys next time