Latest / The Eye Believe Podcast / Eye On Research | Session 2: Adjuvant Therapies – What’s New Today? (And What Can You Do About It!?)

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Eye On Research | Session 2: Adjuvant Therapies – What’s New Today? (And What Can You Do About It!?) · The Eye Believe Podcast

0:00
hey everybody
0:01
thank you so much for joining us again
0:03
here in session 2 I hope it was not too difficult
0:06
for us to get everybody back into the next session
0:09
this is our adjuvant session
0:11
so previously
0:12
we were covering all of the metastatic treatments um
0:15
liver directed and systemic
0:17
and then right now
0:19
we're going to cover our adjuvant section
0:21
and we've got Doctor Carvajal again
0:23
Doctor Jose Lutzky and Doctor Kahn
0:25
and we are so thrilled to have them
0:27
but before we get into that
0:28
I want to just give a huge shout out to um
0:30
some of our first FDA approved therapies that we have
0:34
for uveal melanoma immunocore
0:36
they were able to get Kimmtrak through approval
0:38
that was back in I believe 2021
0:40
somebody correct me if I'm wrong
0:42
but we've got the Kimmtrak
0:43
and then we also have Hepzato Kit
0:45
so each of these websites are their relevant areas
0:48
where you as a patient or caregiver
0:50
can get the most up to date information
0:51
on what centers offer these therapies
0:54
and who they might be for that said
0:56
um thank you again to all of our patients
0:58
anybody who participates in clinical trials
1:00
we really can't get where we are today
1:02
without the use of clinical trials
1:04
and without having um
1:05
our patients in those clinical trials
1:07
so those of you who have had the opportunity
1:08
and have said yes to participating
1:10
thank you so much
1:11
and thank you specifically to some of our sponsors
1:13
who have clinical trials like Ideaya Biosciences
1:15
who was referenced earlier
1:17
and then we have Aura Biosciences
1:19
who they are actively recruiting for their eye trial
1:21
their eye treatment trial
1:22
the compass trial and replimune
1:24
which again
1:25
we spoke about RP2 in the previous session
1:27
if you scan this code um
1:30
you can actually find our most up to date
1:32
clinical trial summary from the Acis team
1:35
that was updated in July of 2025
1:37
it's gonna include all the studies
1:38
we talked about today
1:39
but also everything else that could be out there
1:41
that might be relevant to you as a patient
1:43
or just to kind of keep your eye on that
1:45
so scan this QR code if you choose
1:48
and you can also find that in our website
1:50
if you have any trouble
1:51
just reach out to us and we'll help you get that set up
1:54
alright so next up
1:55
I'm going to introduce our speakers
1:56
and we're going to bring Doctor Carvajal
1:58
Doctor Lutzky and Doctor Kahn into the webinar
2:01
so we've got adjuvant therapies
2:03
what's new today and what can you do about it
2:06
and what kind of what should you as a patient know
2:08
happy to have you here Doctor Carvajal
2:09
do you want to go ahead and introduce everybody
2:11
yeah fantastic
2:12
thank you Danet
2:13
and thank you everyone
2:13
for joining the Metastatic session
2:15
I thought that was a really um
2:16
wonderful discussion
2:18
I'm really excited for this session
2:20
joining us here we're gonna have Dr.
2:22
Lutzky from the university of Miami
2:25
who has been doing work in this space for a long
2:28
long time
2:28
and has been really a pioneer in a lot of respects
2:33
and Dr. Kahn from Northwell Health
2:35
who has also done a lot of work
2:36
in the adjuvant and metastatic setting
2:38
for uveal melanoma so um
2:41
thank you guys for joining
2:42
you know this
2:43
this session I think
2:44
is particularly important
2:45
for the patients and caregivers to know about
2:48
and we have for a long time
2:49
been looking for treatments that we can give
2:51
after treatment of primary disease
2:53
to prevent metastasis right
2:56
that's a critical step in
2:57
increasing the number of patients we're able to cure
2:59
let's prevent the mets let's cure more people
3:02
we've tested a lot of things
3:04
and just nothing has really worked
3:06
and now
3:06
we're in a space where we have effective treatments
3:09
in the metastatic setting
3:10
and that gives us a strong hint
3:12
about things that we should take
3:13
earlier in the disease course
3:14
because if it works in the metastatic setting
3:16
I think there's a better chance
3:17
that it'll work in the preventative setting
3:19
that's how these therapies have been developed
3:21
in other cancers and other disease settings
3:24
and so
3:24
what we want to do
3:25
is give you a snapshot of three programs
3:27
and then leave time for Q&A
3:29
I just wanted to give you a quick update
3:30
on where we are with
3:32
ipilimumab and nivolumab we've talked about this
3:35
in the metastatic setting a little bit
3:37
but where we are in the kind of preventative setting
3:39
and just to to give folks
3:42
you know a lot of you have received these treatments
3:43
Keytruda Opdivo
3:45
the combination of ipilimumab and nivolumab together
3:49
maybe the nivolumab and the relatlimab
3:51
Doctor Letsky has done some work in that space
3:54
um and I think the bottom line is these immunotherapies
3:57
which work very well in skin melanoma
4:00
to the point that it can be curative in that disease
4:02
can work in uveal melanoma
4:05
but it just works less well and less frequently
4:08
and in fact when you look at the number of patients
4:10
in whom we can shrink tumor
4:12
for uveal melanoma these are just for the larger studies
4:15
you know it's maybe 15
4:17
20% of patients that we can get major shrinkage
4:21
that being said there was some activity
4:23
and so um
4:24
based upon that activity
4:26
one of the small pilot adjuvant trials that was done
4:30
led by Dr Rapisuwon at Georgetown um
4:33
was this single arm trial
4:35
so all patients with high risk
4:37
uveal melanoma
4:39
were offered treatment with ipilimumab and nivolumab
4:42
one thing that's really important to discuss is
4:45
how do we define who's at high risk right
4:48
who are the patients for whom we're more worried
4:51
that the risk of recurrence is high enough
4:53
that we want to do a treatment that may be toxic
4:55
and there are a number of different ways that we can do
4:57
this
4:58
you know
4:58
one is just looking at the anatomy of the primary tumor
5:01
how big it is
5:02
you know what structures in the eye are involved
5:04
does it extend beyond on the globe itself
5:08
we can look at the the genes of the cancer and say
5:11
you know does it have different
5:13
you know is there just one copy of chromosome 3
5:15
which tends to um
5:17
be found in tumors where
5:19
we're worried that the risk of recurrence is higher
5:21
or we can do um
5:23
something called gene expression profiling
5:24
and that's the Castle Biosciences assay
5:27
alright friends
5:28
give us just a sec we're having technical difficulties
5:30
we've made it most of the time
5:31
without any of this happening
5:33
so thank you to the internet
5:34
we're gonna send some
5:35
some prayers up to the internet gods
5:37
and um
5:38
Doctor Carvajal will rejoin in just a minute
5:41
for the sake of time though
5:42
Doctor Khan can I have you share your section next
5:45
while I get Doctor Carvajal back on
5:48
yeah sure
5:49
yeah so this is actually good
5:50
it's it's
5:51
you know
5:52
Doctor Carvajal was just starting to talk about
5:54
you know all the different criteria that we use
5:56
in terms of gauging
5:59
who is at higher risk of having a recurrence
6:03
versus who is potentially lower risk
6:05
and you know
6:07
that's what um this
6:08
this table on um
6:10
on on the left shows
6:13
this is actually from a review paper
6:14
that several people that were here today
6:17
worked on
6:18
and I think it summarizes well
6:20
all of those different factors and characteristics
6:23
that we look at when we're trying to think about um
6:27
those factors that may
6:28
predispose someone
6:29
to having a higher or lower risk tumor
6:31
and so there's something called the AJCC stage
6:35
this is like
6:35
a national organization that we use to grade tumors
6:40
by size by features
6:42
that's historically been used across many cancers
6:46
and we do use it in this cancer as well but
6:48
but we've also got these additional tools
6:50
these genetic tools that can help us understand things
6:55
um oh
6:55
keep on going Shaheer
6:58
sorry about that we can circle back um
7:01
so I so
7:03
so there there are these factors right
7:05
and when you you know
7:06
are diagnosed
7:07
and you're talking to your ocular oncologist
7:09
and the medical oncologist
7:11
part of the team you know
7:12
these are the things that we're looking at
7:14
to try to figure out okay
7:15
well
7:16
you know
7:17
what should we be doing as part of the next step
7:19
after the primary treatment is done
7:22
whether that's radiation therapy or surgery
7:25
and you know
7:26
historically the answer has been
7:28
we're gonna do surveillance right
7:29
we're gonna watch and hopefully nothing will come back
7:33
but we're gonna be careful to check for that
7:35
and god forbid something does come back
7:37
we're gonna try to catch it as early as possible
7:39
so
7:39
we have the maximum number of options available to us
7:42
and we were just talking about all those options
7:44
that are evolving actively
7:46
from local therapies liver directed therapies
7:49
systemic therapies and figuring out which one's
7:52
gonna be the right one for you
7:54
but then there's this other question that
7:56
that Doctor Carvajal was just alluding to
7:57
which is
7:59
what if we could prevent that recurrence
8:02
from even occurring and the underlying
8:04
you know question here is
8:06
you know even when the primary treatment occurs
8:08
whether it's radiation or surgery
8:10
we think that there are some folks who have cells
8:13
that have already broken off of that tumor
8:15
and have settled in the body somewhere
8:18
most most commonly in the liver
8:20
and over time they will find a way to start growing
8:25
and so if we could potentially intervene at that time
8:28
when those cells are still very small in number
8:30
before they've had a chance to
8:32
you know really latch on somewhere and start growing
8:35
where our treatments may be less effective
8:38
there's a potential role for giving these treatments
8:41
at that setting and hopefully
8:43
they would be more effective
8:44
and prevent people from having a recurrence
8:47
to begin with and so
8:49
Doctor Carval is gonna talk about one of the trials
8:51
that's already been done
8:52
and it's gonna be assessed further
8:54
using the immunotherapy uh
8:56
but I was going to just spend a couple minutes
8:58
talking about this trial of
9:00
of adjuvant Tebentafusp
9:02
and so in the previous session
9:03
Doctor Carvajal already talked about
9:05
you know the mechanism of Tebentafusp
9:07
and what we've seen
9:09
in terms of the benefit that people have seen
9:12
with that treatment in the metastatic setting
9:15
and exactly because of that benefit
9:18
we're now very interested in seeing
9:20
could we do it in this situation
9:22
where there may be some microscopic cancer
9:26
that we can't see
9:27
and hopefully we can kill those cells at this time
9:29
at that time and then prevent them from growing further
9:32
and so this trial this ATOM trial
9:35
it's um
9:36
you know a pretty unique trial
9:37
and that it's being done all across the world
9:40
and it's being really centered in
9:42
in Europe by this cooperative group called the EURTC in
9:45
in Europe
9:46
and it's a phase 3 trial and so
9:48
part of that design
9:50
is that it's going to be randomized
9:54
so that we can really
9:55
truly assess whether this treatment is effective or not
9:59
with the ultimate goal being
10:00
that
10:01
we're going to prevent people from having a recurrence
10:03
and we're going to you know
10:04
meaningfully improve how people do long term and
10:08
and so you know
10:09
obviously you know
10:10
when you're enrolling on a randomized trial
10:13
there is that potential downside
10:15
that you will be randomized to the control arm
10:18
and I know for a patient
10:20
that could be difficult to deal with all of the
10:23
you know logistical things that we ask
10:25
but really to answer this question
10:28
and to make sure that we're giving this treatment
10:30
and it is proven to be it does prove to be effective
10:34
this is a design that we that we have to do
10:37
so who is this trial gonna be for
10:39
so you obviously
10:41
because Tebentafusp is only effective
10:43
in people who have this certain
10:44
HLA type you have to have that HLA
10:47
A 0 2 0 1 subtype
10:50
you have to be within basically three months of your uh
10:55
radiation therapy or surgery
10:57
and you have to have certain factors with your tumor
11:00
that make us think
11:01
that you might have a higher risk of recurrence
11:04
and so either by these clinical characteristics
11:07
or by these genetic characteristics
11:09
that we know do correlate with
11:11
with higher risk and then what are we gonna do
11:13
well
11:14
we're gonna give people six months of this treatment
11:18
that the tebby in one arm and in the other arm
11:21
people are gonna be observed
11:22
and then we're gonna follow up
11:23
and we're gonna see how people do
11:24
and hopefully
11:25
we're gonna see that most people do really well
11:28
uh but particularly
11:30
we're hoping that that treatment with the Tebentafusp
11:32
actually meaningfully improves how people do
11:36
uh and so that is also illustrated in this figure on
11:39
on the top right that shows what we call the schema
11:42
and gives the kind of time frame
11:43
as well as to what um
11:46
what the study will be looking at
11:48
and then um
11:49
yeah sorry
11:50
I know it's a little bit blurry
11:51
but uh
11:52
uh but
11:53
and then the the last part on the bottom right is um
11:56
you know I
11:57
I mentioned that this is being centered in
11:58
in Europe
11:59
but we are going to be opening it here in North America
12:02
as well and so um
12:04
there's gonna be a total of 11 institutions um
12:07
across the US and Canada
12:09
and here at Northwell
12:10
Doctor Carvajal and myself will be kind of leading it in
12:14
in in this part of the world
12:15
but there will be additional sites
12:18
uh spread throughout the country and in Canada as well
12:21
and so um
12:22
we hope that this study will be um
12:24
opening uh
12:25
very soon within the next few months
12:27
and over the ensuing you know
12:29
six months or so
12:30
hopefully across a wide range of these studies sites
12:33
as well so
12:34
this is a really exciting next phase
12:36
in studying this effective therapy
12:39
and hopefully broadening it
12:41
to the point
12:41
where we can prevent people from having a recurrence
12:44
to begin with
12:44
and yeah
12:45
so I'll turn it over to Doctor Lutzky now
12:47
good afternoon everyone
12:49
so I'm gonna talk about a clinical trial
12:52
for high risk patients that we have recently activated
12:57
at the university of Miami
12:58
but will be activated in a number of centers
13:01
throughout the United States uh
13:04
hopefully very soon
13:05
so this is a trial of this drug quisinostat
13:10
so Doctor Bill Harbour
13:12
who has worked a lot in this field uh
13:15
discovered this gene called BAP1
13:18
and that's a
13:19
that's a gene that is a Braca 1 associated protein
13:24
and it it turns out that this gene is mutated
13:28
in a lot of patients with uveal melanoma
13:31
I'm sure everyone in the audience knows about the
13:34
the Castle test and class 1 and class 2 uh
13:38
patients who are at high risk with class 2
13:42
almost uniformly have mutations in the BAP1 gene
13:47
uh so uh
13:48
while studying this BAP1 gene
13:51
the Doctor Harbour's lab
13:53
it was found that these mutations
13:55
caused the BAP1 gene to lose its function
13:59
uh so when that happened
14:01
the risk of uveal melanoma coming back increased
14:04
so he looked
14:05
and I'm not gonna go through the whole thing obviously
14:08
but you know
14:08
through extensive search for drugs that could mimic the
14:13
some of the functions of BAP1
14:15
he came down with this drug
14:16
called quisinostat
14:17
so this drug has gone through phase 1 trials
14:21
been found to be safe
14:22
and in some experiments in his lab
14:26
he looked at 2 mouse xenografts
14:29
these are human uveal melanoma cells
14:32
they are uh
14:34
inserted in the subcutaneous tissues of mice
14:37
and you can see at the bottom really um
14:40
can I point yeah
14:42
can you see my pointer
14:43
so there is the is the best way to see
14:45
so the bottom are uveal melanoma tumors
14:50
the the two on the left are from uveal melanomas
14:55
they had a back on mutation
14:56
and the one on the right was from uveal melanoma
15:00
a tumor that did not have a BAP1 mutation
15:03
the tumors on top of that
15:05
are the ones that were treated with quisinostat
15:08
you can see that the BAP1 mutated tumors
15:11
did not grow when treated with quisinostat
15:15
and the one that was not
15:17
bapoin mutated mutation mutated
15:19
did not seem to to mind quisinostat at all
15:22
you know showing that indeed maybe uh
15:25
we are uh mimicking some of the functions of uh
15:29
the BAP1 gene that are important for uveal melanoma
15:32
the primary objective of this trial
15:34
is to see if we can reduce or delay
15:38
the occurrence of distant metastasis
15:40
the so called distant metastasis free survival
15:42
in patients that are high risk
15:46
for a recurrence with uveal melanoma
15:49
and
15:49
and those patients are the patients that are class 2
15:53
or that have tumors that are 12 millimeters or greater
15:57
in what we call the longest basal diameter
16:01
so looking at a very large database from
16:05
from the Collaborative Ocular Oncology Group
16:07
of over 1500 patients we determined that at 36 months
16:13
about 60% of the patients were free of metastasis
16:17
meaning that 40% had developed metastasis
16:20
in this
16:21
the study was powered to detect
16:23
an absolute 15% improvement
16:26
in the distant metastasis free survival
16:29
from 60 to 75% or or better
16:32
in terms of secondary objectives
16:34
we're going to be looking at
16:36
a lot of additional factors
16:38
that are listed here
16:40
and I'm not really going to go into that
16:45
we're also going to be doing a number
16:47
of correlative studies
16:49
with some of the blood that we'll be drawing
16:52
along the study so it's an open label
16:55
it's a single arm it's a multicenter study
16:58
and we are going to be using a synthetic control arm
17:02
which is means that we're going to go to that database
17:05
and find patients
17:06
that are similar to the patients that are in our study
17:10
and we're going to use
17:12
what's called propensity score methods
17:14
which is a method to adjust the variable so that the
17:18
the patients are comparable
17:19
it's not a randomized trial
17:21
but it's as close as we can get
17:23
without actually doing a randomized trial
17:26
so this has opened at university of Miami
17:30
we have four or five patients
17:32
and we're really striving to open this quickly
17:37
in the other center so aside from us
17:40
duke university georgetown northwell
17:44
mass general dana-farber Northwestern
17:47
University of Texas Southwestern
17:50
and the Angeles Clinic
17:52
are going to be participating in the trial
17:54
so I think we have a lot of geographic coverage
17:59
that patients
18:01
most patients will be able to find a center near them
18:05
if they want to participate
18:07
awesome thank you
18:07
Doctor Lutzky
18:08
what Doctor um
18:09
Lutzky was talking about regarding that study design
18:12
and comparing things against
18:14
you know a set of patients from before
18:17
so Doctor Rapisuwon
18:18
did the same thing with that IPI Nivo trial and
18:21
and what was really striking was
18:24
when you look at the patients
18:25
who were enrolled on that trial
18:27
it would have been expected that
18:30
you know about 60% of the patients
18:32
would have actually had the cancer come back
18:34
within three years
18:36
right so I think it was something like
18:38
you know it was expected
18:40
that 42 or 43% of the patients would be doing well
18:43
without recurrence um
18:45
but what he actually saw in that trial
18:47
is that 70% of patients were doing well at three years
18:50
without recurrence
18:52
um which was really
18:53
really striking there were issues with the trial
18:56
there were side effects that
18:57
that had to be managed and so forth
18:59
but just looking at how well uh
19:01
it seemed to work compared to historical controls
19:03
was really striking
19:05
um it's not definitive
19:07
and so doctor Rapisuwon's next step is really to see
19:10
can we build a randomized trial
19:12
that would definitively answer the question
19:14
does this treatment help or not
19:16
and he's currently working
19:17
through one of the NCI cooperative groups
19:20
to see if we can actually launch that trial
19:22
and so the hope is that we
19:23
we will be able to have that launch in the next
19:26
it'll be a few years honestly
19:28
but but at least it's in the works
19:30
awesome
19:31
our first question is question about the ATOM trial
19:35
do you know when immunocore will open sites in the US
19:37
for the phase 3 ATOM adjuvant Tebby trial
19:41
yeah Doctor Khan
19:42
do you want to take that yeah no
19:43
so we're we're
19:44
we're hoping to be open very soon at Northwell
19:46
and you know
19:47
each site has their own processes to open but um
19:51
we're hoping to be open
19:52
within the next couple of months
19:53
at Northwell and then followed shortly thereafter by um
19:58
most of the other sites in
19:59
in some in some order
20:01
okay awesome
20:02
so you guys are all medical oncologists
20:03
so correct me if I'm wrong
20:04
but my understanding is that
20:05
once we have an FDA approved medicine
20:08
like Tebentafusp is now FDA approved
20:10
when it goes through trial
20:12
um it
20:12
it becomes a little easier for it to push out
20:14
more rapidly um
20:16
because it's already been approved
20:17
and some of the sites are already equipped
20:19
to do the procedure
20:20
or to do the type of treatment that there is
20:22
so when they do start circulating sites
20:25
my assumption is gonna be
20:26
that they're gonna start to pop up pretty quick
20:28
yeah I think so
20:29
I mean I think there's certainly less um
20:31
roadblocks
20:32
sometimes with established agents than with new agents
20:34
and so yes hopefully
20:35
I mean there are still
20:37
you know factors
20:38
because this is a new setting right
20:40
and so we're not doing this as standard of care
20:42
and um
20:43
it's not approved for this purpose
20:44
and so it still is investigational
20:46
and so
20:46
you still have to go through all of these processes
20:48
to make sure we're doing all of this properly and um
20:52
the right monitoring and everything
20:53
but you're right yeah
20:54
hopefully this won't be um
20:56
a laborious process at most sites
20:58
okay uh
20:59
this question is asking are there any studies
21:02
adjuvant studies for patients who are HLA negative
21:04
and Doctor Lutzky
21:05
if I'm wrong correct me
21:07
but was the um
21:09
the trial that you mentioned
21:10
the quisinostat
21:12
is that how it said is that one HLA specific
21:15
or is it for anyone who is it
21:17
or is it BAP1 specific
21:19
uh quisinostatis not HLA specific
21:22
it's for any any HLA no
21:25
okay so
21:26
Tebentafuspis really the only HLA
21:28
adjuvant trial we have right now
21:29
that would be relevant there
21:30
Ipi Nivo not gonna be applicable
21:33
and the quisinostat
21:34
is also not going to be HLA dependent
21:37
OK
21:39
Doctor Lutzky
21:40
is there any limitation for patients to join
21:42
the quisinostat
21:44
oh my gosh
21:45
quisinostat study
21:47
is there any limitation for patients to join
21:49
like if they were coming off of another adjuvant trial
21:53
yes they
21:54
they cannot have been in another adjuvant trial
21:58
this has to be their first adjuvant trial
22:02
and there's not like
22:04
room for adjuvant trials there isn't room for like
22:06
compassionate use correct
22:08
well uh I
22:10
we we have not done any compassionate use for
22:13
for that drug we remember
22:14
we don't have any evidence that it works
22:17
so it would be kind of hard to
22:19
yeah that's kind of what I was thinking
22:20
is that if it's not like I think compassionate use or
22:23
like use out
22:24
you know outside of some of the trial stipulations
22:27
is it's only gonna happen in the metastatic setting
22:29
at this point yeah
22:30
Danet some of the vaccine trials
22:33
that have been kind of open for melanomas
22:36
including uveals have been very permissive in terms of
22:40
you know
22:40
what treatments people might have received before
22:43
um and so
22:44
there are definitely people with uveal melanoma
22:45
who've gotten some sort of treatment
22:47
and then gone on to some of these vaccine trials
22:49
where what they're looking for is
22:51
does the vaccine actually activate the immune system
22:53
as opposed to whether the vaccine helps prevent it from
22:58
the cancer from coming back
22:59
okay um
23:01
well do you guys have any like
23:02
just kind of from the
23:03
the circle of the adjuvent studies
23:05
why is this so exciting
23:07
to have these adjuvent therapies
23:09
to have I think it
23:10
we have at least three specifically
23:12
and hopefully there will just continue to be more
23:15
I think Dr
23:16
Carvajal did we talk
23:17
I
23:18
I feel like I talked to somebody about even the use of
23:20
um the use of Hepzato in an adjuvant setting
23:23
is that something that's being noised about
23:26
yeah Jose
23:27
do you wanna yes
23:29
there I I think the
23:30
the company is uh
23:33
thinking about having uh
23:34
an adjuvant trial um um
23:38
so that that will add another potential option
23:42
um um
23:43
so
23:46
I think
23:46
I think it's exciting that we have all these trials
23:49
you know we couldn't even think of an adjuvant trial
23:52
just a few years ago because there were no drugs
23:55
that appeared to have any activity with
23:58
unfortunately there
23:59
there are enough patients for all of these trials
24:03
we should be able to have them all completed
24:06
so I think it was
24:07
when you and I were just talking separately Dr
24:10
Carvajal but you mentioned one of the kind of areas in
24:13
in comparing uveal melanoma to say
24:15
the cutaneous melanoma
24:17
treatment landscape the adjuvant
24:19
is kind of
24:20
where things started to really come together
24:23
for cutaneous melanoma so in your opinion
24:26
like why is us having these adjuvant trials
24:28
so important for the future
24:30
of treatments metastatic and
24:31
and everywhere yeah
24:32
I'm so excited I mean
24:34
it wasn't too long ago where
24:35
in cutaneous melanoma it really wasn't that long ago
24:38
where we didn't have anything that worked that well
24:40
but then once those targeted therapies
24:43
the new immunotherapies came on board
24:45
you know within the span of like
24:47
not even a decade right
24:49
you're you're seeing major improvements and outcomes
24:53
cures when they couldn't be achieved before
24:56
and so now we're in a place where we have
24:59
you know Tebentafusp
25:01
which we know meaningfully helps people live longer
25:03
we have um
25:05
you know percutaneous hepatic perfusion
25:07
which does a really good job
25:09
shrinking the tumor in the liver
25:10
and controlling it for a long time
25:12
we've got new drugs in development
25:14
the Darovasertib story and others
25:17
you know so if we can prove
25:18
and we are show testing
25:20
whether those work in the metastatic setting
25:22
you know if they work in that setting
25:25
you know maybe they'll work in the preventative setting
25:27
and so now
25:27
we have really good things
25:29
to take into the adjuvant setting
25:31
that are I think
25:31
really exciting
25:33
yeah I agree
25:34
I think it's so exciting to see the movement um
25:37
and I think that
25:37
that is really where the hope for patients is right
25:41
that we we can see that there's movement happening
25:43
in the landscape of treatments um
25:46
showing that you know
25:48
when you come into this diagnosis
25:49
you're not just gonna feel like
25:51
oh well yes
25:52
all we can do is watch and wait
25:54
like there's
25:55
now there's some options
25:56
and there's some really clinically data driven options
26:00
um obviously there's still gonna be kind of
26:03
you know these are trials
26:04
so that means they're volunteer basis
26:05
your doctor is not gonna say
26:06
oh yeah
26:07
you absolutely can just go and do this
26:09
but hopefully when we can prove that they work
26:12
then that will be kind of the standard of care
26:14
right like that we would go okay
26:16
your eye was treated that's great
26:17
well we know that you've got this level of risk
26:20
and so we're going to put you on this treatment
26:22
or this one or this one
26:23
you know whatever it
26:24
it turns out to be based on the genetics
26:26
or just all of the answers
26:27
that will come together in time
26:29
as the as the physicians who do these trials
26:31
and who are researching like
26:33
they pull everything together
26:34
and then we will have better direction
26:37
and I think that's
26:37
that's the most exciting part about all of this
26:40
it's so exciting I wonder if it's worth commenting
26:42
on the neo adjuvant space
26:44
and what's going on there
26:45
yeah so can you explain what neo adjuvant is
26:48
right so
26:49
I know we we covered adjuvant like
26:51
metastatic is obviously when you're metastatic
26:53
adjuvant before you're metastatic
26:55
so what's neo adjuvant
26:57
I don't know Shaheer
26:57
do you want to take that one
26:58
yeah sure
26:59
so I um
27:00
I think and
27:01
and to echo
27:02
you know everything that's been said
27:04
I think you know we
27:06
I think the difference between maybe
27:07
like five years ago and now is
27:08
you know like Doctor Carvajal was saying
27:10
we have treatments that have been proven to be
27:13
you know have some activity and efficacy
27:15
and now we're testing them earlier on right
27:17
so it's not it was never a shot in the dark
27:19
but it was you know
27:21
with more limited support
27:22
and now we have more robust support to
27:24
to actually to actually be optimistic
27:27
about the likelihood
27:28
that these adjuvant trials are gonna work and
27:30
and corresponding in the neo adjuvant setting
27:32
right and so um
27:34
Neo adjuvant is before any sort of definitive treatment
27:38
right and so um
27:41
in in uveal melanoma
27:42
the definitive treatment is
27:44
either the radiation therapy
27:45
or the surgery and we know that for
27:47
you know a good number
27:47
of people that's gonna be curative
27:49
that's gonna eliminate all of the cancer
27:50
and it's not gonna come back
27:52
uh unfortunately
27:53
for some people it does
27:55
and so for that group of people
27:57
we're doing these adjuvant trials
27:59
but we're also looking to see
28:01
could we potentially reduce that risk
28:04
alter that profile by giving some treatment up front
28:08
before any sort of radiation or surgery occurs
28:12
um and there's quite a bit of momentum behind this idea
28:17
in other cancers
28:18
including in skin melanoma and cutaneous melanoma
28:20
where there's some really exciting data that's come out
28:23
that this these immunotherapies like Ipi Nivo
28:26
if you um
28:28
if you get just a few cycles of it before surgery
28:31
to remove the cancer
28:32
and maybe a lymph node that's involved you
28:35
and you have a good response
28:36
when we look at it under the microscope
28:38
that might
28:39
predict you having a much lower risk of a recurrence
28:42
down the line
28:44
and so the and one of the kind of
28:47
elegant parts of doing this treatment up front is
28:50
you know we can sometimes
28:52
then see what is happening in the tumor uh
28:55
what is the response to the treatment
28:57
where was we can't really do that
28:58
when we're giving it in the adjuvant setting
29:00
right because we're treating these microscopic cells
29:02
that we can't measure or assess
29:05
um
29:05
but when we do it before surgery or radiation therapy
29:08
we can potentially do another biopsy
29:11
if it's surgery we can look at the tumor
29:13
and we can say okay
29:13
what did that period of treatment do
29:15
whether it was six months of the Ideaya medication
29:18
Darovasertib or um
29:21
you know something like Tebby or something else um
29:24
we can then get a concrete assessment and
29:27
and maybe that does then add to our understanding
29:29
and our knowledge
29:30
about what the risk is going to be moving forward
29:33
and then obviously
29:34
ultimately
29:35
it improves the chance that the cancer never comes back
29:38
so there's yeah
29:39
there's a variety of efforts
29:40
the the one that's ongoing right now is
29:42
is Darovasertib
29:44
and uh
29:45
there's gonna be some data
29:46
that's gonna continue to be presented and
29:49
and maybe a phase 3 trial that will be happening soon
29:51
but then some other efforts as well
29:54
so I know how the the Darovasertib um
29:58
trial works the neo adjuvant setting it's
30:00
it's typically only been used for larger tumors
30:03
to prevent enucleation is that correct
30:06
yeah so
30:07
you know they've
30:07
they've had to kind of like
30:10
because this is all new in
30:11
in uveal melanoma they've had to kind of
30:13
think critically about how to assess
30:16
you know what they're going to look for
30:17
and so you know
30:19
one way and
30:19
and ultimately I think what we all care about um
30:22
is to assess how people do long term right
30:25
that can take a long time
30:26
and hopefully if people don't have a recurrence
30:29
it can take a very long time
30:31
and so to get a concrete assessment as to
30:33
you know whether there's benefit
30:34
whether there's some activity
30:36
related to this medication
30:38
they've looked for some other markers
30:40
like does the tumor shrink
30:42
does the radiation therapy field decrease
30:46
does the need for surgery to remove the tumor go away
30:50
and maybe we can just treat it with radiation therapy
30:52
and then
30:53
they're also looking at things like vision outcomes as
30:55
as time goes on so yeah that's
30:58
that's how they've designed it right now
31:00
we'll see exactly how things are in the phase 3 trial
31:02
but the purpose is still to
31:05
you know maximumly benefit people
31:07
by really preventing the recurrence
31:08
but also by looking at some of these other
31:11
what we call surrogate markers
31:13
okay that makes sense
31:14
alright well
31:15
you guys this has been so fun
31:17
I'm sure we could talk for hours about all of this
31:19
but um
31:20
Doctor Lutzky Doctor Carvajal
31:21
do you guys have anything else you want to add
31:22
just to round this out
31:25
yeah I
31:26
I again want
31:27
want to uh
31:29
echo everybody's uh excitement
31:31
uh in this area uh
31:33
we have a targeted therapy neoadjuvant
31:36
we have a what we call epigenetic trial
31:40
which is the quisinostat
31:42
trying to change the way that
31:44
that genes are expressed to improve outcomes
31:47
we have immunotherapy uh
31:49
with Ipi Nivo
31:51
and uh Tebentafusp
31:53
so uh
31:54
I think patients now they're high risk
31:57
have all these choices
31:59
and
31:59
these trials are going to be done all over the country
32:02
they should be able to find a center
32:04
where they can have their treatment
32:07
in a way that's not disruptive to their lifestyle
32:11
I think
32:11
we're trying to make an effort to make sure that um
32:15
people have access to these trials across the study
32:18
across the country right
32:20
so if it's not one trial
32:21
then it's gonna be another trial
32:23
but we're trying to make sure that people have access
32:25
as best as we're able to
32:27
yeah and that access is something that
32:28
I mean I
32:29
I participated five years ago in a
32:31
an adjuvant study myself
32:33
and I was required to travel at that point
32:35
and so you know
32:36
just know that
32:37
there may be some travel associated with this
32:39
but if you have a shot right
32:42
if you have a shot at going from high risk
32:43
to reducing that level of risk for metastasis
32:46
is why not take it right
32:48
like I mean
32:48
that's kind of how I looked at it
32:50
is that I would rather have done something than
32:51
felt like a little bit of a sitting duck as a patient
32:54
because once you learn more about
32:56
you know
32:56
what the biopsies mean and
32:57
and what the prognostic data from our castle testing
33:01
or any of those
33:02
it can feel a little scary
33:03
and so to have things that you can do as a patient
33:06
it feels very empowering and to know that
33:08
you know we've got doctors like
33:09
these wonderful doctors on
33:10
and many of the other doctors around the country
33:13
who are trying to make sure that patients know
33:14
they have these options for the adjuvant setting
33:17
I think it's it's so critical
33:19
and it's so important
33:20
and if you're listening and you're maybe
33:22
you know a year
33:22
two years into your your treatment
33:24
your eye
33:25
please just keep an eye out right
33:27
maybe one in some cases
33:29
keep an eye out for those new patients
33:31
who are coming into our community
33:33
and who maybe don't know about this
33:35
they don't know about the adjuvant studies
33:36
or maybe
33:36
they just haven't quite linked up
33:38
with the right medical oncologist yet
33:40
um it is really tricky when you're a new
33:42
new patient navigating this metastatic setting
33:44
and so just let's look out for each other
33:46
and let's make sure that
33:47
if there are new patients coming in
33:49
who might be able to participate
33:51
in one of these kinds of clinical trials
33:52
even if it's not you send someone who could benefit
33:55
because this could really um
33:57
having them participate
33:58
could really change the landscape for everybody
33:59
in the future of uveal melanoma
34:01
Dr. Lutzky
34:02
Dr. Dr. Khan
34:03
thank you so much for being here
34:05
and for your knowledge and and um
34:08
slides that you shared thank you
34:10
thank you thank you
34:11
Danet
34:12
and thank you to A Cure In Sight for putting this together
34:14
thanks again to our sponsors
34:16
who made this whole presentation possible
34:19
we could not do this without Castle Biosciences
34:21
Ideaya Biosciences Aura Biosciences
34:24
Immunocore and Delcath Systems
34:26
their financial support of these kinds of seminars um
34:29
is really the way that we're able to produce
34:31
produce this and to find speakers and to make sure that
34:34
you know
34:34
this all goes out to you on the internet in hopefully a
34:37
you know glitch free way the
34:39
the best that we can
34:40
we also just want to encourage you guys
34:42
if you didn't know we have the Insight Registry
34:44
and I didn't even like
34:45
should let Doctor Carvajal talk about this
34:47
but um he also has the Omni Registry
34:49
which is a physician led registry
34:51
for metastatic disease
34:53
and these are like a registry basically
34:55
is one of the best ways that we as patients
34:57
can contribute to ongoing research
35:00
and to current research
35:01
so if you have not yet joined the Insight Registry
35:03
please consider doing so
35:05
scan the code or head to insight dot
35:07
I am rare dot org and you can do um
35:10
everything you can to share your
35:11
your personal medical history
35:13
and to share your personal experience with doctors
35:15
and just improve the way that care goes for us
35:18
as patients as well as um
35:19
talk about you know
35:20
what are you doing how is treatment going now
35:22
if you're in metastatic treatment
35:24
this is gonna be critical
35:25
and we're at we're past our five year point
35:27
so we're to the point where the data has
35:29
what they call matured
35:30
and that means that we're able to collaborate
35:32
with other registries and make use of that data
35:35
so it's really exciting make sure to join the registry
35:37
if you have not yet done so
35:39
and to start answering those surveys
35:41
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35:42
subscribe to our monthly newsletter
35:44
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35:46
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35:48
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