Latest / The Eye Believe Podcast / Eye On Chopin Webinar | The Eye Believe Podcast

Transcript

Eye On Chopin Webinar | The Eye Believe Podcast · The Eye Believe Podcast

0:00
hi everybody
0:00
welcome to our Eye On The Expert webinar series
0:03
thank you guys for joining us
0:05
and for registering ahead of time
0:06
so that you could be part of our webinar
0:08
today we're gonna be joined by three different guests
0:11
and um
0:12
we had a slight change in program this week
0:14
and we are delighted to have Doctor Chmielowski
0:16
who is a medical oncologist from um
0:19
from UCLA and his kind of co conspirator
0:23
so to speak in the Hepzato world
0:24
Doctor Padia who is an interventional radiologist
0:27
and we are also joined
0:28
from all the way on the other side of the um
0:31
of the country at the East Coast from our
0:33
from Boston Mass General Hospital
0:36
and that is Doctor Kam Montezari
0:38
so um
0:38
I'm gonna bring them on I'm gonna bring my screen down
0:41
um in just a second
0:42
but as I bring them into the webinar
0:44
I just wanted to make sure to
0:46
to thank all of you guys here who are listening
0:48
and just also send a massive
0:50
massive thanks out to our sponsors
0:53
um our webinar sponsors are
0:54
who make this possible for us to produce
0:57
to plan ahead of time to have the registration platform
1:00
and then to just kind of get the word out to all of you
1:03
so those of you guys who are listening
1:04
would love to hear in the chat where you're from
1:06
and if you're here as a patient or as a caregiver
1:09
as a practitioner we
1:10
would absolutely love to hear where you're at
1:12
and just have you guys interact in the chat
1:14
Doctor Padia
1:14
is going to present a little bit of the data
1:16
about the Chopin study so uh
1:19
the Chopin study sorry
1:20
we're gonna all learn how to pronounce this
1:22
we're gonna all learn how to pronounce this study
1:24
but it came out in ESMO in 2025 and um
1:27
our goal here is to kind of
1:29
just share those study insights
1:31
but also to help you guys as patients
1:34
as caregivers learn um
1:35
kind of some different ways
1:36
that doctors in the uveal melanoma treatment space
1:39
are personalizing metastatic treatment
1:42
using the theories using the science
1:44
using you know
1:45
the data that we have to support
1:46
following the Chopin protocol
1:48
um these doctors
1:49
are people who have been utilizing Hepzato
1:51
for a really really long time
1:53
um I guess it's been out for almost
1:55
we're coming up on three years
1:56
I think as far as FDA approval
1:58
and each of them has kind of unique processes
2:01
and how they do this and reasons why they do it
2:03
and I'm super excited to have all of them on
2:05
to answer questions for the audience
2:09
those of you guys listening
2:10
but also to answer the questions that I have in plan
2:12
or have in have in mind
2:13
have planned
2:15
anyway so thank you guys again for being here
2:18
uh and I think
2:19
let's go ahead and get started
2:20
with Doctor Padias presentation
2:22
if that's okay um hi
2:25
good morning Danet
2:25
thanks again for um
2:27
for the invitation I'm just gonna share my screen here
2:30
mm hmm
2:34
alright
2:36
Danet can you see it OK
2:38
I can yes
2:38
it looks OK so
2:39
good morning everyone so what I'm gonna do uh
2:41
my name is Sid Padia
2:42
I'm an interventional radiologist at uh
2:44
the university of California Los Angeles
2:47
um I work uh
2:48
hand in hand with uh
2:50
Bartosz Chmielowski who's here as well
2:52
who's our medical oncologist
2:54
who sees most of our patients
2:56
um and I'm gonna talk about a new clinical trial
2:59
that just resulted in late 2025
3:02
called Chopin
3:04
so I'll go over the overview
3:06
and then I'm gonna kind of digress in the beginning
3:09
to try to give you like
3:10
a two minute overview of liver directed therapies
3:13
which is kind of what I've focused my career on
3:16
so this is kind of the title
3:18
it's obviously a long title for the Chopin study
3:20
um this was a single center study
3:23
it was done in the Netherlands um
3:26
and it was randomized
3:28
now when we talk about liver directed therapy it's
3:32
you could see it's kind of like this alphabet soup
3:35
a lot of this depends on not just
3:39
you know
3:39
how patients or people present with their tumors
3:42
but even institutional or operator preference
3:45
so for example
3:47
at UCLA we tend to have a little bit more bias towards
3:50
uh something called Y90 radio embolization
3:53
as well as the Hepzato procedure
3:56
also known as percutaneous hepatic perfusion PHP
3:59
but other institutions
4:00
may do things a little bit differently
4:02
so it's just kind of different flavors
4:05
so in brief
4:06
um many patients who have liver metastases
4:10
from uveal melanoma will get an arterial therapy
4:13
and what that means is we put a catheter
4:15
typically at the top of the thigh
4:17
um through a tiny little incision
4:20
and we uh
4:20
use X ray guidance to get that catheter into the artery
4:23
up to the tumors and we deliver something
4:25
and that deliver
4:27
whatever that something is is there to kill the tumor
4:30
kill the metastases so sometimes uh
4:33
we can do something called taste
4:35
which is uh
4:36
transarterial chemo embolization
4:38
the chemo that is used is called bcnu
4:41
you can develop you can also um
4:43
infuse a immunomodulating agent called GMC SF
4:48
and um
4:48
what we typically do at UCLA is we
4:50
our preference institutional preference
4:52
and operator preference
4:53
is to do something called a Y90 radio embolization
4:56
where we infuse radioactive beads into the tumor
5:00
via the artery to kill them as well
5:02
and all of these have I would say
5:05
advantages and disadvantages
5:07
for each and every patient
5:09
now let's go back to the Chopin trial
5:11
so what was this trial this trial was patients with um
5:15
so every patient every trial
5:17
has what's called an inclusion and exclusion criteria
5:19
so it's important that you know
5:21
all of us you know
5:22
in the medical world we always look at the IE
5:24
or the inclusion exclusion criteria
5:26
so
5:26
when we're trying to apply this trial to our patients
5:29
we want to make sure that um
5:31
they're kind of the same match
5:33
so I think some of the
5:34
I didn't list all the inclusion criteria here
5:37
but the main thing is that these people had to have had
5:40
um metastases to their liver
5:43
that's at least predominantly in the liver
5:45
additionally you could see this uh
5:48
less that less than 50% by volume
5:50
so in other words
5:51
if your liver is completely taken over by tumors
5:54
everywhere you're not really a candidate for this uh
5:58
trial it was really uh
5:59
meant for people with
6:01
lower than 50% of the liver is taken up by tumor um
6:05
and you could have gotten prior uh
6:08
treatment such as chemo embolization
6:10
that's TACE or Y90 radio embolization
6:13
also abbreviated as SIRT
6:15
so they looked at um
6:17
standard endpoints um
6:19
and this is again a little bit alphabet soup here
6:22
but um
6:23
what we what we often do
6:24
is look at what's called the primary endpoint
6:26
which was um
6:27
basically how you were doing at one at one year
6:30
at 12 months
6:32
the enrollment was designed for 76 patients
6:35
so what they did was
6:36
they did what's called a randomization
6:38
so you you sign the consent
6:39
you enroll and
6:40
for those of you who have enrolled in clinical trials
6:42
you you know how that works
6:43
but if you haven't you know
6:44
then a basically a computer uh
6:46
randomly allocates you to
6:48
let's say in this case
6:49
group 1 or group 2 and in Group 1
6:53
you got the Hepzato procedure
6:54
that's abbreviated PHP that's called
6:57
that stands for percutaneous hepatic perfusion
7:00
and
7:00
I'll show you a couple of pictures of how that works
7:02
for those of you who have not received it
7:04
um and so that you can see that top row
7:07
they got randomized to PHP at week one
7:10
and then you go all the way to week 7
7:11
and you get another round
7:12
which is typically what we do
7:14
alternatively
7:16
you could have gotten PHP plus immunotherapy
7:19
now in this case um
7:21
the immunotherapy was kind of
7:22
I would say the standard of care in most patients
7:25
especially when the trial started
7:27
and that's ipilimumab and nivolumab
7:30
um all the
7:31
the trade names in the United States are Opdivo and
7:34
Yervoy Bartos did I get that right
7:36
is that OK I'm not an oncologist
7:38
so I'm trying to you know
7:39
learn um
7:40
and so you can see the scheme here
7:42
so they got like a dose of Ipi Nivo
7:44
that's a that's through an IV in your arm
7:47
and then you get the PHP the next week
7:49
and then you get two more rounds of Ipi Nivo
7:51
and then you get another PHP
7:53
and then you get another round of Ipi Nivo
7:54
okay so
7:55
that the goal was to compare
7:57
people getting the Hepzato procedure
7:59
or PHP versus people who get combination
8:04
in other words PHP plus immunotherapy
8:07
and see which one does better
8:10
okay
8:10
I'm gonna step back and just give a 2 minute overview
8:14
of what is Hepzato or also known as PHP
8:18
this is kind of a schematic diagram
8:21
the procedures are done in the hospital
8:24
they are done under anesthesia
8:25
so you're completely asleep
8:27
the procedure itself including anesthesia time
8:30
takes about three and a half hours
8:33
we at UCLA did a patient yesterday
8:36
you know my procedure time was 2 hours
8:38
10 minutes total anesthesia time
8:40
plus procedure time was about 3 hours
8:43
20 minutes so that
8:44
that's kind of your time frame that you're looking at
8:46
and then afterwards um
8:49
we uh
8:50
keep people in the hospital for one night
8:52
and then just discharge them in the morning
8:54
so all of this are done through pinholes
8:57
and by pinholes I mean um
8:59
the incisions are typically like an eighth of an inch
9:03
maybe a little bit smaller than an eighth of an inch
9:06
there are um
9:07
three of them primarily
9:09
one is in the left upper thigh
9:10
one is in the right upper thigh
9:12
which you can kind of see on the schematic here
9:13
and one is at the base of your collarbone
9:15
on the right side
9:17
um the goal here is on the left side
9:21
where you can see that syringe that
9:23
that's that catheter that goes into your artery
9:26
and then it goes into the artery
9:28
going into your liver
9:29
and that's where we're infusing the chemotherapy
9:32
and the chemotherapy is called melphalan
9:34
then on the bottom right leg
9:37
or excuse me
9:38
on the right leg
9:39
you have another catheter that's in the vein
9:41
so that vein that catheter is again
9:44
by catheter I mean like
9:45
kind of hollow bore plastic tube
9:47
um it has two balloons
9:49
which you can see right in the middle of our
9:51
of this Powerpoint image and what that does is
9:54
it isolates the veins in the liver
9:57
and it's on a withdraw
9:58
so it sucks the blood from the veins
10:01
it sends it through this box and through these filters
10:05
which you can see on the left side of the screen
10:06
and what those do is it extracts out the drug
10:11
it returns your blood back into another catheter
10:14
in your vein at the base of your collarbone
10:16
so basically it's like a 3 60
10:19
you know circuit where it's filtering out the
10:21
the chemo so
10:23
the entire purpose of this
10:24
is to deliver high dose of chemotherapy into the liver
10:28
and you take out the extract
10:30
so it does not spread throughout your body
10:33
and as a result
10:34
about 1 to 2% of the drug that we give ends up
10:39
what's called systemically
10:40
or in the rest of your body and
10:41
you know the rest of it gets filtered out
10:43
so it's it tends to be very safe
10:45
um this is kind of another cartoon and uh
10:48
schematic of how this procedure works
10:51
uh there is a company that makes this entire device
10:53
and the drug
10:56
and then again we isolate the liver
10:59
um we saturate the liver with the chemotherapy
11:03
and then we filter out the chemotherapy with this um
11:07
circuit
11:09
so I'll give one example
11:10
this is a patient not on that trial
11:12
but kind of similar progressing on immunotherapy
11:15
you can see this is um
11:16
this is an MRI kind of three images from his same MRI
11:20
just high medium and
11:22
and like kind of the low part of the liver
11:24
that big gray structure with the white lines is the
11:28
is the liver and um
11:30
everything in the yellow those are tumors
11:32
those are uveal melanoma metastasises in his liver
11:36
and what we do is this is his chest X ray on the left
11:41
and you can see this catheter
11:43
coming in from the patient's right
11:45
um collarbone and so on
11:48
and then the catheter is coming in on the right
11:50
the right image is of his abdomen
11:52
the catheter is going north from the legs
11:56
um
11:57
this is kind of a picture of how it looks in our room
11:59
you can see it's kind of a zoo
12:01
there's like I would say 10 to 12 people doing this
12:04
so it's not a one man show
12:05
this is a big team effort
12:07
we have a lot of um uh
12:10
physicians uh technologists
12:12
nurses uh
12:13
working hand in hand
12:14
so I think the hardest thing about setting this up uh
12:17
at not only at UCLA
12:18
but every program was
12:19
was getting everybody on board and to work together and
12:22
and to act as a team
12:24
so I won't I'll try to speed through this
12:26
but this is a picture of what's called an angiogram
12:29
you can see this catheter going north
12:31
from the bottom of the image
12:32
to the middle of the image
12:33
the black stuff is contrast dye
12:35
similar to what you may have gotten in a cat scan
12:38
and these all these lines
12:39
these black lines are arteries in the liver
12:42
and those are the
12:43
the red arrows are where we're gonna infuse the drug
12:47
and this is that balloon
12:48
this is the balloon in the veins
12:50
and this is isolation of it
12:52
and I'm gonna show a video
12:54
um so on the left video
12:56
this is us injecting the contrast
12:59
and it's going into the right side of the liver
13:01
and that's the hepatic artery
13:04
so that's where we're going to deliver chemo
13:06
and at the same time we're delivering chemo
13:09
we have these balloons in the veins
13:11
and again we inject contrast
13:13
these are the veins and you can see it's completely
13:15
isolated between the balloons
13:17
so the chemo will get delivered
13:19
through the hepatic artery
13:21
catheter on the left perfuse through the liver
13:24
and then get excreted into this vein
13:26
which you see on the right
13:27
but you these balloons have trapped it
13:29
so the that
13:30
that chemo doesn't escape into the rest of the body
13:35
so that's it in a nutshell
13:36
and I'll kind of now jump back to the Chopin trial
13:40
and show you kind of the the data
13:43
so the inclusion criteria I talked about um
13:47
and you can see that again
13:48
they were randomized to PHP or PHP plus immunotherapy
13:54
now there's always this patient characteristic table um
13:58
in in the beginning
13:59
and I would say that come some of the things to note um
14:02
most patients
14:03
did not have any significant prior treatment
14:06
so 90% or 82% had no prior treatment uh
14:11
for their liver metastases
14:13
I'm not talking about what they had in their eye
14:15
but in their liver metastases
14:17
the other thing is that 90% um
14:21
of the patients had metastasises
14:24
that was in their liver only okay
14:26
so only 10% of the patients had
14:29
for example
14:30
lymph node or in their bone or in their lungs and so on
14:33
so these are things
14:33
that we always wanna take into account
14:35
when we're trying to use this data
14:37
whether it's from the IR side
14:38
or from the medical oncology side
14:40
to use to our patients
14:41
because we wanna make sure that it's relevant
14:44
I'll give you an example if someone comes in
14:46
and they have a lot of lung metastases
14:48
but very few liver metastases
14:50
you know then
14:51
you know Doctor Chmielowski asked
14:52
and I ask ourselves does this trial really fit them
14:55
and it may not it may not
14:58
okay the first thing we always look at is safety
15:01
we always want to make sure that any trial
15:03
any drug any therapy is safe
15:06
and when we look at this
15:08
there was definitely a higher rate of complications
15:13
and what we call we term those as adverse events
15:15
and we have grading systems in the
15:17
in the oncology world like grades one through five
15:21
and kind of our benchmark is grade 3 or worse
15:24
so you can see in the two columns
15:26
like the second row grade 3
15:29
treatment related adverse event
15:31
was much higher when you combined the therapies
15:34
now what gets lost in these numbers is most of these um
15:38
adverse events were very temporary
15:41
they were correctable and so you did have a like
15:43
let's say a drop in your counts or
15:46
let's say your
15:47
your blood counts or your white blood cell count
15:49
but it was fixed but we still record that
15:52
so that's important to know that
15:54
you know most of these were not necessarily permanent
15:57
or really didn't affect you in a
15:59
in a real or physical way
16:03
okay
16:04
second thing we always look at is how did the tumors do
16:06
in other words did your tumors stay the same
16:09
did they get bigger or worse
16:11
or did they get better and
16:12
we often look at these things called waterfall plots
16:15
so on these plots the uh
16:18
each vertical bar is a single patient
16:22
and you can see kind of like the
16:24
the midline that's at zero
16:26
and if you went above the bar
16:29
that mean and that's
16:30
those are the ones um
16:31
predominantly on the left side of those charts
16:33
that means that your tumors grew
16:36
and if you went below the bar
16:38
that means your tumors shrunk obviously
16:41
so you can see that for each individual
16:44
and then the top one is patients who got both therapies
16:47
immunotherapy plus PHP
16:49
the bottom is the ones who got PHP only
16:53
and you can see that a couple things
16:55
number one
16:56
most patients actually had their tumors shrink
17:00
there is a handful that had their tumors grow
17:02
which you can see on the left side
17:03
which is um
17:04
you know unfortunate
17:05
but the good thing is most of them had shrink
17:07
when you combine it that's the top one
17:10
only two patients had their tumors grow
17:13
and everyone else um
17:15
did pretty well
17:16
like there you can see in the blue and the green and
17:19
you know the
17:20
the on the right side of the graph
17:21
there were some people who had
17:23
went to minus 100 what does minus 100 means
17:25
that means on the follow up scans
17:27
their tumors disappeared
17:29
so
17:29
we use a kind of a benchmark called objective response
17:32
or response rate and that's on the bottom uh
17:36
in the red box so the um
17:38
with Hepzato alone or PHP alone
17:41
the response rate was 40%
17:43
which is what has been seen in other trials
17:46
and when you combine it with the immunotherapy
17:49
now we're getting 76% and
17:52
which is way higher than to my knowledge
17:55
at least any clinical trial reported for uveal melanoma
18:01
um there we do this um
18:03
other analysis and I'll kind of try to wrap it up
18:05
in the interest of time
18:06
it's called kaplan meier survival curves
18:09
and so you can see the blue
18:10
so the uh on the bottom
18:12
the X axis is that's time
18:14
and then the y is like overall survival
18:17
so you want it like try to be as flat as possible
18:19
in theory so the blue is the combination arm
18:23
and they did better
18:23
so you can see that those curves are separated out
18:26
so I think this is um you know they
18:28
they did show us what's called a survival benefit um
18:33
both at one year and at specifically at two years
18:37
so some of the take away points
18:38
this is what I think we're gonna discuss
18:40
you know it seems like it's well tolerated
18:42
although it does have a higher adverse event rate
18:44
when we combine the immunotherapy and the PHP
18:48
um the tumor response
18:50
in other words do your tumor shrink
18:53
uh is
18:54
is much higher than any therapy
18:56
whether it's liver directed therapy or systemic therapy
18:59
that's been seen in the past
19:00
which is I think
19:01
promising
19:01
and that we saw an increase in survival as well
19:05
um we're gonna have a lot of discussion on this
19:08
but you know the
19:09
the really
19:09
the questions that remain in my practice
19:10
can I use this algorithm with any
19:13
any immunotherapy this was Nivo plus Ipi
19:17
there are other immunotherapies that you may be on
19:19
or you may have heard of uh
19:21
some of them have recently come out
19:23
you know can it be
19:24
can you use these results
19:25
and just kind of apply it for that
19:27
um there's another one called Tebentafusp
19:29
also known as Kimmtrak that was not used in this study
19:33
because it was not available in the Netherlands
19:35
at the time of the study start
19:38
so can you use these results
19:40
and kind of
19:40
just extrapolate them to people on Kimmtrak
19:43
we don't really know these things
19:45
and also the the number of rounds of PHP
19:48
and the systemic therapy were limited
19:51
in the trial they only did a few
19:53
and that was a little bit for practical reasons
19:55
and financial reasons so
19:57
in patients who get four or five
19:59
or even six rounds of PHP
20:01
or a lot of people who get nivolumab and ipilimumab
20:06
you may get both
20:07
and then you get on what's called a Nivo maintenance
20:09
so you get it like a the infusion
20:11
like every few weeks for a much longer time
20:14
they didn't get that in this
20:15
so if we did that would we get even better results
20:19
and that's it thanks so much
20:21
thank you so much Doctor Padia
20:23
Doctor Padia actually has come back multiple times
20:25
both as a guest on the podcast
20:27
and for previous webinars
20:28
and last February he was a part of the
20:31
puzzling out liver directed therapies
20:33
and he spoke um about Hepzato as well as
20:37
you know other interventional radiology things
20:39
and then we've got a few videos on our YouTube channel
20:41
if you are not aware that we have a YouTube channel
20:43
go subscribe uh
20:45
and you can listen and see
20:46
and he goes into really really
20:47
really strong detail on how Hepzato works um
20:51
and as an interventional radiologist
20:52
performing the procedure and I mean
20:54
Doctor Padia
20:55
how long have you been doing this specifically at UCLA
20:57
yeah so
20:58
good question the um
20:59
procedure got FDA approved in um
21:01
late 2023
21:02
it became commercially available in the United States
21:04
April 1st, 2024 we did our first patient April 10th
21:09
like 10 days later
21:10
after commercial approval
21:12
we've now done 65 procedures in about 25, 28 patients
21:19
um we are currently averaging
21:21
maybe four to six per month right now
21:24
and I'm trying to remember
21:24
I feel like you and doctor Chmielowski
21:27
you both were kind of the
21:30
one of the first commercially available sites um
21:32
if not the first commercially available sites
21:34
and so you know
21:35
like he's
21:36
he's definitely a person to go listen to
21:38
on the YouTube channel about how the procedure works
21:40
so that said um
21:42
you're right it's a party
21:43
I mean I've had Hepzato
21:44
so those of you guys in the
21:45
in the audience if you have had the Hepzato treatment
21:48
just on its own the
21:49
the PHP please drop it in the chat
21:51
let people know like
21:52
if you've had this procedure
21:54
I actually have my sixth procedure coming up next week
21:56
so yay me
21:57
um but
21:59
I'm super excited for us
22:00
to get to talk a little more about
22:01
kind of what this is
22:02
why this might be
22:04
and a lot of what we're going to be talking about here
22:06
is going to be based on these doctors
22:08
you know personal experiences
22:09
and what they're seeing in practice
22:11
but also some of this is theory right
22:13
some of this is we're
22:14
we're kind of hypothesizing and guessing as we go
22:17
and hoping for the best
22:19
because of the results that we have
22:20
um but the first question I wanted to lead off with
22:22
to um
22:24
to all of you I suppose
22:25
is the Chopin trial
22:26
is this a trial that patients today can enroll in now
22:31
because
22:32
I think that this is a big misconception right now
22:34
and um
22:35
so Doctor Montazeri do you
22:37
do you wanna answer that one
22:39
yes so um
22:40
I think there was first a question in um
22:43
in the chat about what uh
22:44
immunotherapy was used um
22:46
which Doctor Padia mentioned
22:48
but again it was ipilimumab and nivolumab
22:51
we usually uh
22:52
use the uh
22:53
higher dose of ipilimumab as standard of care
22:56
and lower dose of nivolumab
22:57
in this trial interestingly
22:59
they used uh
23:00
the flip dose which was the lower dose of ipilimumab
23:03
1 mg per kg and a higher dose of nivolumab or Opdivo
23:07
which has lower toxicity rates
23:09
and that was one um
23:12
I think smart move on um
23:14
the um trial design uh
23:16
which um
23:18
is uh basically helpful um
23:20
to know if we can spare a lot of patients the toxicity
23:24
the high rate of toxicity and immunotherapy um
23:27
to your question Danet I forgot your question
23:30
so my question is the Chopin trial
23:32
is one that I'm hearing noised about by patients asking
23:35
oh can I be part of this trial
23:37
and I think that that's a
23:39
that's a valid question um
23:41
but it's one that hopefully we can
23:43
yes so this uh
23:45
study was done in Europe and was completed as um
23:49
Doctor Padia mentioned about 37
23:52
38 patients on each arm of the study
23:55
it was not a huge study
23:56
but it was very helpful answering a lot of questions
23:59
um so um
24:01
you don't necessarily need to get enrolled on the trial
24:05
if you present to one of the centers that are
24:08
that have expertise in doing PHP
24:11
um again
24:12
it's an multidisciplinary
24:15
basically treatment
24:16
and we usually um
24:18
try to work as a team
24:20
and we work very closely with our colleagues
24:22
in interventional radiology
24:23
you can get the treatment outside of the clinical trial
24:27
in a
24:28
basically a standard of care
24:30
because both of these treatments have been approved
24:33
and the trial showed that it's overall safe um
24:36
for the patients um
24:37
and it adds benefit
24:39
this study
24:40
is not open to accrual this certain study
24:42
there are similar studies
24:43
for example
24:44
there is a Swedish group that are looking to
24:47
seeing if maintenance therapy with nivolumab
24:49
would add benefit or there are studies looking to um um
24:55
seeing if additional P H P
24:57
treatment would add benefit
24:59
yeah so I guess the big
25:01
you know the big takeaway for you guys listening is
25:03
you can ask your doctor about this here in the States
25:07
or you know
25:07
wherever PHP treatment is available um
25:10
cause
25:10
I know we have it commercially available in Europe
25:12
and also in the United States
25:14
um but you can ask to follow this protocol
25:17
maybe would be a better way for us to like
25:19
kind of talk about it in the future um
25:20
for today without feeling like oh
25:23
like I'm gonna be limited
25:24
because it's a trial and I can't do the trial um
25:27
so that's an important distinction to know
25:29
um are you guys good if we get into some of the
25:32
kind of maybe the theoretical why
25:34
as to why this all looks as good as it does
25:38
yes because like
25:39
this is my favorite part I'm not even
25:41
I'm not even joking you guys
25:42
this study came out and I
25:44
I mean as a personal patient
25:45
who's also receiving PHP treatment
25:47
and who had already kind of
25:50
kind of pulled my doctor into hey
25:52
let's follow the Chopin protocol
25:53
even though we don't have the results officially yet
25:56
um I was thrilled to see these results
25:58
and um
25:59
I think one of the biggest reasons
26:00
is that it can feel so much
26:02
for those of us who don't qualify for Kimmtrak
26:05
or who don't qualify for trials that have um
26:08
like prame positivity or HLA status
26:11
like kind of as a
26:12
as a stipulation for if you can join the trial
26:14
it can feel a lot like we
26:16
as the patients are a little bit of a sitting duck
26:18
um so let's kind of dive into maybe the why
26:21
um and I know we can't spend a ton of time on this
26:23
because this is theory but
26:25
why do you guys each think
26:27
that combining the Hepzato treatment
26:30
with an immunotherapy
26:31
can produce a stronger response than either of them
26:34
separately
26:35
um doctor
26:37
Chmielowski
26:38
do you wanna go ahead and take that
26:39
yeah let me take it in
26:40
so of course
26:41
you know one of the big questions
26:42
would we still ask you know
26:44
what would be the outcome
26:46
if the patients received the Hepzato first
26:48
and then immunotherapy followed
26:50
of immunotherapy first and Hepzato followed
26:53
this is much easier
26:54
possibly associated with fewer side effects
26:57
or should we combine it so
26:59
assumption why the combination might be better is
27:03
uh we know that immunotherapy
27:05
uses the immune system to fight cancer
27:07
and this immunotherapy with nivolumab ipilimumab
27:10
has been extremely successful
27:11
in treatment of cutaneous melanoma
27:13
but uveal melanoma is a very different disease
27:16
we now although they carry the same name of melanoma
27:19
when you look at the biology of these diseases are very
27:22
very different we apply the knowledge
27:24
from cutaneous melanoma to uveal melanoma
27:27
very often
27:28
but we saw that the response rate to nivolumab
27:31
ipilimumab is much lower in uveal melanoma
27:35
than in cutaneous melanoma
27:38
so for for immunotherapy to work
27:41
you have to have a perfectly working immune system
27:44
that can destroy your cancer
27:46
but the cells that are destroying the cancer
27:48
have to have a target
27:50
and have to be present in the tumor environment
27:52
for them to work
27:55
so very often we see
27:56
then if we can maybe injure the tumor
27:59
and release the particles from the tumor
28:02
this would be a better chance for the immune system
28:05
to recognize something that should be destroyed
28:08
so this is a simplistic way
28:10
by using
28:11
by using PHP we hope that we do a
28:15
we cause injury to the tumor
28:17
and this indirectly will stimulate the immune system
28:21
we are pre priming this immune system
28:24
with immunotherapy before we do PHP
28:27
so the immune system is already prepared to do
28:31
to do its job and to destroy cancer
28:34
of course there could be very
28:36
a lot of criticism
28:37
it's a little bit of theoretical approach to
28:40
you know approach to
28:41
to what our explanation what I'm
28:43
what we see
28:44
but definitely this trial confirmed than a combination
28:49
a combination immunotherapy is probably the
28:53
a combination immunotherapy
28:54
and liver targeted therapy is the way to go
28:57
advantage also of this approach
28:59
is when
29:00
immunotherapy provides the treatment to the whole body
29:03
so if you if you have the disease outside of the liver
29:07
or possibly you can develop in the future
29:09
immunotherapy can not treat not only your liver
29:12
but treats your whole body
29:14
which gives an additional point
29:16
to improve the hopefully outcome
29:21
I feel like that was such a good explanation
29:23
thank you haha
29:25
um Doctor Montazeri as
29:26
as in a fellow like medical oncologist
29:28
do you have anything that you wanna add
29:29
and then Doctor Padia I would love to ask what you
29:32
cause I sorry
29:33
I like
29:34
I get very I'm very excited about this
29:36
so we have one question
29:37
before we continue talking about this
29:39
that I feel like we can we can kind of address now
29:41
just so that people have this as a background
29:43
um one of the questions from an attendee is
29:45
are doctors starting to use this combination
29:47
instead of only PHP right now
29:49
as a result of the Chopin trial
29:52
Dr Montazeri and Dr um
29:54
Doctor Padia Doctor Chmielowski
29:56
like as far as I am aware
29:58
you guys have been following something similar to this
30:00
kind of you know unintentionally
30:03
um but obviously now
30:05
you know we have the study results to work with
30:07
so um
30:09
yeah so
30:10
I mean go
30:11
I guess if you want to go ahead and speak to that yeah
30:13
Doctor Chmielowski
30:15
explained beautifully um
30:17
we know that something happens with PHP in the liver
30:20
that's immune activating
30:22
and helps immunotherapy work better
30:24
now the question is
30:25
what is the best sequence of the treatment
30:28
should we first start with PHP
30:29
or start with systemic immunotherapy to prime the body
30:33
um the answer is we don't know um
30:36
and we're looking into this um
30:38
we are at our center also doing a study
30:42
that includes biopsy of the liver lesion
30:47
before and after PHP treatment
30:49
to see what happens in the molecular level
30:53
and the tumor microenvironment
30:54
and liver microenvironment
30:56
and that may help answer the question
30:57
as to why PHP can be immune activating um
31:02
in a real world experience
31:05
we know that we need at some point at least
31:08
both systemic therapy and liver directed therapy
31:11
for multiple reasons because systemic therapy
31:14
unfortunately doesn't work as well inside the liver
31:17
because of a lot of barriers
31:18
because of mechanical barrier
31:20
because of press the um basically
31:22
the external pressure
31:23
from the tumors to the vasculature
31:26
and um decrease basically um
31:29
vascular perfusion to the tumor um
31:32
environment and so
31:33
there is mechanical barrier
31:35
in delivering the drug effectively
31:36
if you're doing only systemic therapy
31:38
to the liver lesions and also
31:41
there is barriers inside the liver
31:44
because of how immune suppressive
31:46
the liver environment has been designed naturally
31:51
because of the role of the liver for the body
31:54
to detoxify everything um
31:56
and um so we know that the combination um
32:00
usually works better even if liver directed therapies
32:04
which are interventional
32:05
radiology colleagues do beautifully um
32:08
benefit the patients um
32:10
to control their intrahepatic or their liver lesions um
32:16
unfortunately at some point
32:18
there will be disease progression outside the liver
32:21
so that's why in experience
32:23
we tend to combine both of these
32:27
and sometimes without large data
32:30
just based on our own experience
32:32
we get to combine different types of systemic therapy
32:37
wet liver directed therapy
32:39
yeah absolutely
32:40
um and I think it's
32:42
it's so important for us as patients
32:44
to recognize that
32:45
there are doctors who have been aware of this
32:48
kind of I mean I
32:49
I guess it sounds from what you guys are saying
32:51
it sounds like
32:52
maybe there's some level of synergistic effect
32:54
like that they're working
32:55
you know together kind of in tandem
32:58
because of you know
32:59
the the properties of the immune system
33:01
that you both explained
33:02
and that ability for them to work together
33:04
gets kind of heightened by combining them
33:07
in some fashion and the
33:09
the Chopin study
33:09
is one example of how that combination has looked
33:12
um so let me just add one
33:15
you know a few few
33:16
just few words you know
33:17
so we've been combining immunotherapy with Hepzato
33:21
since day one of our you know
33:22
the since our first procedure
33:24
you know we uh
33:26
from the beginning uh
33:28
I did not see necessarily
33:30
a compelling reason not to combine them
33:32
so why to wait for progression
33:34
if we can get benefit of possibly both therapies
33:37
and you know
33:38
I'm was really
33:40
waiting for the results of the Chopin trial
33:42
because actually
33:43
the trial confirmed not only when you can
33:45
we can do it but probably
33:47
you are improving the outcome by doing it together
33:50
you know we've been doing kind of an Assumption
33:53
you know then
33:53
I want to get the benefit of
33:56
to give a benefit of both therapies
33:58
to our to our patients
34:00
but try to confirm this is the right way to go
34:04
yeah I think just to add to that
34:05
you know nothing really
34:07
from a scientific perspective
34:09
in terms of which one goes first
34:11
and how do you combine a lot large time
34:13
many times it comes down to just
34:14
patient and institutional logistics
34:17
um you know
34:18
these are
34:19
these are pretty challenging procedures to set up
34:21
let's say for us at UCLA we
34:23
you know you
34:23
you have to undergo some kind of a work up
34:25
a cardiac work up and so on and uh
34:27
maybe insurance authorization for the
34:29
both the immunotherapy and the PHP
34:32
so sometimes you know
34:33
which one comes first ends up being
34:35
not necessarily a scientific decision
34:38
or a medical decision but more just a real life
34:41
you know this is how it's gonna happen
34:43
because this is just how the chips fell
34:46
um so we've got
34:48
obviously lots of questions coming in
34:50
and I feel like there's a few of them
34:51
that I wanna address a little bit later
34:53
so I'm gonna kind of gloss over those for a minute
34:55
um but let's talk like you guys have talked and
34:59
and mentioned you know
35:00
the the timing and trying to figure out
35:02
like how do we use this in real time
35:04
um what are some of the potential advantages
35:06
and disadvantages that you guys are seeing
35:08
in practice of using Hepzato
35:10
earlier in a patient's metastatic journey versus say
35:13
you know when they're more progressed
35:15
um cause I think that there's definitely
35:17
you know especially after the
35:19
the focus trial there's definitely been this kind of
35:22
noise in the community that oh
35:24
like Hepzato is for later down the road
35:27
so have you guys noticed anything
35:29
you know potential advantages
35:30
disadvantages
35:30
or what do you maybe potentially hope to see
35:33
um I'm not sure who
35:34
actually would be the best one for this
35:35
so raise your hand if you're up
35:38
so I can I can talk to about it
35:40
in the context of other liver directed therapies
35:43
we still do let's say
35:44
for example quite a bit of um
35:46
ablation or Y90 radio embolization
35:49
um we kind of worked out our own algorithm at UCLA
35:53
and it's not necessarily treating patients with PHP
35:57
early or late in their course
35:58
but it's we look at
36:00
the factors we predominantly look at are tumor size
36:03
tumor number tumor location
36:04
and how many
36:05
and that allows us to stratify and triage people
36:09
I'll give you two kind of more extreme examples
36:11
someone who presents with um 25
36:14
30 very small
36:16
you know tumors that are size of my thumb
36:18
scattered throughout the liver
36:19
they're gonna need a whole liver kind of therapy
36:22
whatever that is you take that in contrast to
36:25
another person who has who presents with a single
36:28
you know tumor that's two inches uh
36:32
you know like 5 cm
36:33
like this big um
36:35
in the corner of the liver
36:36
and then the rest of the liver is
36:38
does not have anything
36:39
those two people are gonna get in
36:41
in my view are gonna get different things
36:43
the the guy who has
36:46
who needs a whole liver treatment
36:48
the PHP procedure is really well suited
36:50
for someone who needs a whole liver treatment
36:53
the person who has a single tumor
36:55
is going to get something much more focal
36:57
and that in our experience
36:59
tends to be a typically a Y90 radio embolization
37:02
and if that person develops multiple tumors
37:07
down the road they may not
37:08
but if they do let's say it happens in six months
37:11
or 12 months or two years
37:12
then we can also offer the Hepzato procedure
37:17
at that time the nice thing
37:19
fortunately what we found
37:20
is that whether you do the PHP after the Y90
37:25
or the Y90 after PHP
37:26
or you put in an ablation in between those
37:28
there doesn't seem to be any adverse interaction
37:31
like it doesn't pile up
37:32
uh I've
37:34
I've had patients who've gotten 3
37:35
4 Y90s and then they went to a PHP
37:37
I've had people who went from a PHP
37:39
and then they got two Y90s
37:41
and I don't I haven't seen any um
37:43
additive at uh
37:45
side effects or toxicity
37:46
so the nice thing is we are able to like
37:48
kind of mix and match it
37:50
this tends to be a little less scientific
37:53
when we do this
37:53
it goes into the weeds and it becomes a little
37:55
this is where kind of uh
37:56
I would say the art of medicine
37:58
it is uh
37:59
it plays a big role
38:01
yeah absolutely
38:02
um Doctor Montazeri
38:03
what are what are you seeing
38:05
I guess in practice you know
38:07
of utilizing immunotherapy in combination with PHP
38:10
at Boston Mass Gen
38:12
yeah absolutely
38:13
and I think uh
38:15
as Doctor Padia mentioned it um
38:17
at the end
38:18
comes to tailoring the treatments to each patient
38:21
um one thing to keep in mind is that most of the time
38:25
unfortunately we don't get to cure the disease and uh
38:29
we end up controlling the disease
38:31
so one thing that I keep in mind
38:33
is that we have to line up as many potential
38:37
effective
38:38
treatment options as possible for the patients
38:41
um so if uh
38:42
there is a promising um
38:45
upfront clinical trial
38:46
that may not be available after this type of treatment
38:50
that's something to consider um
38:52
as um
38:54
also it was pointed out um
38:56
if the patient has had a prior liver
38:59
directed therapies or other systemic therapies
39:01
we always have the option of using a Chopin
39:06
plus different types of systemic therapy in the future
39:09
so it's a better that we start from a um
39:13
clinical trial that may benefit um
39:16
the patients in terms of controlling the disease
39:18
or shrinking it or helping patients live longer
39:22
and also add quality of life
39:23
and to them upfront um but again
39:27
at the end it also depends on um
39:29
you know each person's situation
39:32
each person's disease burden
39:33
and the urgency of you know shrinking the lesions
39:36
let me add few words only
39:38
so even among my colleagues
39:41
you know sometimes I see
39:42
you know we ask the question
39:43
and very often patients ask
39:45
if you're gonna use everything up front
39:47
what's else left afterwards
39:50
so this is a common question
39:51
so if you used you know
39:53
your PHP and your immunotherapy upfront
39:55
and then it didn't work or stopped working
39:58
and this what are you gonna do next
40:01
but I always argue but if
40:04
if your patient is going to live longer by doing this
40:08
means then
40:08
it will need a longer time
40:10
for you to use something else
40:12
so why do you
40:13
why do you worry so much about what's gonna happen next
40:17
if you know if it will take you a longer time
40:20
or maybe they don't need the next
40:22
you know maybe this is too optimistic by saying that
40:24
but no
40:25
I mean as a patient myself
40:26
I feel this um
40:28
and I know like
40:29
Doctor Padia um
40:30
I think in the in the Chopin study
40:32
you kind of referenced um
40:33
and I think all of you have referenced
40:35
some of those future studies
40:36
like the ones that are currently being done
40:38
you know in other areas um
40:39
where they're looking at okay
40:41
like can we figure out
40:42
is it
40:42
better to do the immunotherapy first versus the PHP
40:45
but there are also studies of
40:47
can we do the six rounds of PHP right
40:49
six rounds of Hepzato
40:50
take a break for whatever duration of time
40:52
and then introduce it again later
40:54
like is that
40:55
is that safe is it
40:56
is it feasible is it healthy for the patient
40:58
does it help um
41:00
I think those are questions
41:01
that having an FDA approved treatment
41:03
and having FDA approved like
41:05
clinically available treatments allows
41:07
that kind of like what Doctor Padia said of
41:10
like thinking outside the box and the art of medicine
41:12
it allows you guys to like
41:13
really create these custom plans
41:16
for each of the patients that you see uh
41:18
and I think that that's a huge benefit
41:19
for
41:20
just having those FDA approved treatments on the table
41:22
for sure um
41:23
but like
41:24
Doctor Montazeri does bring up a good point that
41:27
I mean there are still trials
41:29
um the trials can be helpful
41:31
they could be helpful down the road
41:33
they could be helpful in the moment
41:34
and there's it's really
41:35
really hard to know um
41:37
what specifically
41:38
is gonna be the most help to each patient
41:41
I know uh
41:42
just from a patient perspective
41:44
making that decision for me has come down to
41:46
what do I want out of my current life right
41:49
what do I want today to look like
41:50
what do I want tomorrow to look like
41:52
and I have chosen you know
41:54
a route that I feel like affords me what I want in that
41:57
in that path forward and
42:00
but that's gonna look different for everybody
42:01
everybody has everybody has different perspectives on
42:04
on what they want um
42:06
I'm gonna support what Doctor Montazeri said
42:09
you know just
42:10
is we do have clinical trials
42:12
so very it's a natural question from the patient
42:15
so if you have this treatment and showed it worked
42:18
why would you offer me a clinical trial
42:21
which is an experimental therapy
42:23
and I always say you know
42:25
because I want to say you know
42:26
I want to give you
42:27
as many treatment options as possible
42:30
so if this clinical trial can
42:32
we can do now and then what's available later
42:35
this gives you more options in case one doesn't work
42:37
so this is just an argument
42:40
so yes absolutely
42:41
sorry I just wanted to point out that
42:42
as both of you mentioned
42:44
it's definitely a shared decision making
42:47
and we want to make sure that when the patient um
42:51
you know comes to clinic both um
42:54
you know
42:54
with help of our interventional radiology colleagues
42:58
we usually have a multidisciplinary meeting and uh
43:02
try to make sure that you know
43:04
everybody has a good understanding of their options
43:07
and what may be um
43:09
in the future
43:10
so we make together the best decision for each person
43:15
yeah that makes sense
43:16
so while we're kind of on this like
43:17
leg of clinical trials and like OK
43:20
how how could this
43:21
the Chopin trial um
43:22
and the results from this
43:24
and kind of applying this in clinical practice
43:27
how could this affect the future
43:29
clinical trial eligibility
43:30
um so what I'm hearing from you guys right now is that
43:33
you know as of right now
43:35
there are definitely trials
43:36
that have exclusion criteria
43:37
that would make doing you know
43:39
following the Chopin protocol
43:41
more challenging
43:42
for entering a clinical trial later down the road
43:44
is that correct
43:47
it is it is correct
43:49
it is correct right now
43:50
some of the trials exclude this procedures
43:53
and it is of course
43:55
when you write a clinical trial so
43:57
you know it is always a complicated process
44:00
you have to have more strict inclusion
44:02
exclusion criteria
44:04
uh so you can get reliable results of a
44:08
of a of a clinical trial
44:10
and also as
44:12
although the number of centers that can offer PHP
44:15
is growing you know
44:17
it's still somewhat a limited number
44:20
it's not available in every country
44:23
so if you mandate PHP before that
44:27
this might be
44:28
the clinical trial might not be available to many
44:30
many people in the world hmm
44:33
yeah that's a good point
44:34
um so I guess my question
44:36
maybe just naively as a patient
44:38
is as we have something that
44:40
you know has the potential
44:41
of taking two standard of care therapies
44:43
and being used in tandem right
44:45
the the Chopin protocol
44:47
so to speak
44:48
is there room for the future of clinical trials where
44:52
you know somebody could follow this protocol
44:54
as standard of care therapy
44:56
and then enter a trial later
44:58
if that standard of care therapy fails down the road
45:02
yeah absolutely
45:03
I don't know Dr Chmielowski
45:04
do you wanna answer or should I start
45:08
I think and you know that um
45:10
in reality um
45:12
because this is a field um
45:14
that has had um
45:16
less uh
45:17
treatment option and options in it
45:19
that's why we have um
45:21
clinical trials mainly in the front line setting
45:24
that will change in the future
45:26
once we have more FDA approved options available
45:30
and um
45:32
it will hopefully be more inclusive for the patients
45:36
um
45:37
there are trials coming up
45:40
and in the near future
45:41
that are gonna be available after PHP
45:43
after immuno therapy and I hope that in the future
45:46
the way the studies are designed
45:48
they allow patients to have had multiple options
45:51
in the past I think we got to remember that
45:53
this Chopin data got presented in November of 2025
45:58
it hasn't even been published yet
45:59
it's in press right now so it always takes
46:03
uh as Bartosz mentioned
46:04
it takes forever to actually
46:06
you know from the time
46:07
like if the three of us were to design a trial today
46:11
by the time we enroll the first patient
46:12
it's like 18 months right
46:14
I mean it takes a very long time
46:15
it's very painful to to
46:17
it's very painstaking to do these trials
46:18
so I do hope um that all the new trials will allow this
46:24
because I I do think it's
46:25
you know
46:25
when we're starting to see response rates of 75%
46:29
to tell patients
46:30
you can't get this if you wanna be on a trial
46:33
while I understood that two years ago
46:36
when we didn't have this level of data
46:38
this level of numbers
46:39
I personally feel like it's a little bit unfair
46:42
so unless the trial has medications or drugs
46:46
that could make someone um
46:49
really sick because they got the PHP um
46:52
in other words they're really worried about um
46:55
an interaction with prior PHP I
46:58
I feel like the the new era 2026
47:01
and going forward they're gonna have to
47:02
I think the the the
47:04
the sponsors of these trials
47:05
and the people who designed them
47:06
are gonna really have to try to accommodate
47:09
this procedure at least in their armamentarium
47:13
yeah I mean
47:13
I would love to see that just
47:15
just as a patient myself
47:17
because I mean
47:19
everybody's
47:20
everybody's story as a patient is so different
47:21
everybody listening we each have such unique journeys
47:25
with metastatic disease
47:26
some people haven't even started the journey
47:28
with metastatic disease and um
47:30
and correct me if I'm wrong
47:31
but is there any noise in the
47:33
kind of in the Hepzato space of using Hepzato
47:36
kind of more adjuvantly saying OK
47:38
you've got a class 2 patient
47:40
we're gonna treat you with one or two Hepzatos because
47:43
like this is
47:44
this has been my my catch 22 on Hepzato all the time
47:47
and I talk about this till like
47:48
I guess I'll talk about it till I'm blue in the face
47:50
it's there to treat what we can't see right
47:54
so if we can't see the metastatic disease
47:56
before it metastasizes to me
47:58
it makes total sense that this could be an option
48:01
adjuvantly but I understand like
48:03
that's complicated yes
48:06
well it's actually
48:07
the most important thing
48:07
is that you said it's complicated
48:08
and I think part of it is that this is
48:11
this is a big procedure it was um
48:13
when we started this at UCLA in 2024
48:17
it was a massive undertaking um
48:20
uh to get this off the ground
48:23
and it is very involved um
48:26
you know it uh
48:27
it is not like uh
48:29
it is not easy to do it is not easy to set up
48:32
it takes you know
48:33
you saw some of the pictures of my presentation
48:34
there's there's 15 people in the room
48:36
so we have to show if we were to do something like that
48:39
we would definitely have to show significant value um
48:43
and and benefit
48:45
and if we show just like
48:46
a small benefit like this
48:48
we're not I'm
48:49
I'll be honest I'm not interested in this
48:50
we're interested in home runs
48:53
you know we're interested in big leaps
48:55
because this is in my personal opinion
48:57
I'm the guy who does 99% of them
48:59
here it it is
49:01
it's very tough to do these procedures um
49:04
that's why as Kam said
49:06
you know it's not available at every center
49:08
it does take an infrastructure
49:09
it takes a huge team to do this
49:11
so we have to make sure
49:12
that we are going to have a significant chance
49:14
of benefiting people if we offer this therapy
49:18
but I do agree you know
49:20
then an attempt to use it
49:22
maybe in the adjuvant setting would be of of interest
49:26
you know of course
49:28
one of the problems which we face
49:29
we don't even fully know
49:31
how to identify patients who are at high risk
49:34
you know traditionally when
49:35
and we we are guilty of it too
49:37
we kind of repeat old data
49:39
saying that
49:40
half of the patients will develop metastases
49:42
this every paper starts with that
49:44
you know which is probably not true
49:46
because more than data say yes
49:48
the high risk patients
49:50
half of them will develop metastases
49:51
but not everybody is such a high risk
49:53
and
49:55
yeah I keep saying that
49:56
maybe there is something in Southern California
49:58
when in my hands
49:59
only 20 to 25% of patients develop metastases
50:03
and not half you know
50:06
but so I just say so each center defines
50:09
not saying each country so who is the high risk
50:12
how to really predispose so you
50:14
you are not exposing people who have
50:17
who are possibly already cured
50:19
with the local therapy on their eye
50:21
to this to the therapy which is associated with
50:24
you know cost
50:25
about side effects and everything
50:27
but if we can define better
50:29
you know if this people high risk people
50:32
then I think adjuvant treatment would be interesting
50:36
to see if we can delay or prevent
50:37
development of liver metastases
50:42
do either of you um
50:42
Doctor Montazeri Doctor Padia
50:44
have anything else to add
50:47
not really that's well said
50:48
I wanted to say one more thing guys
50:50
you know it's a
50:51
sorry I've been talking so much
50:52
but the one thing is
50:53
I wanted to just show some optimism because
50:56
you know when many patients will come
50:58
and they are already diagnosed with a uveal melanoma
51:02
upfront or they are already
51:03
or later on
51:04
they may be diagnosed with metastatic disease
51:08
they open the internet and say oh
51:10
my median survival is 12 months
51:13
it means I'm gonna be dead in 12 months
51:15
you know
51:17
and then this immunotherapy doesn't work
51:22
it says it doesn't work and
51:25
this procedure is associated with so many side effects
51:29
as we try to point out every journey is different
51:32
every patient is a different story
51:34
but we do have patients who do well
51:37
you know
51:37
and we do have patients who are alive three and five
51:41
and seven years later you know
51:43
and um
51:45
and so this 12 months what you saw somewhere
51:50
it's probably not true
51:51
there will be people who have very aggressive disease
51:53
and no matter how aggressive you want to be
51:55
we will not be able to help them
51:58
but there are patients and our therapies
52:00
and the combinations and sequencing
52:02
and development of new trials and new therapies
52:06
really we are making a difference
52:08
and the patients with your disease can live longer
52:11
yeah I love that absolutely
52:14
um
52:16
I love these words of wisdom from Dr Chmielowski
52:19
yes that's um um
52:22
what we share with our patients
52:23
that these are mainly historical data
52:26
when there was no effective therapies
52:30
times are changing there are newer
52:32
and more effective treatments coming along
52:34
and we all have like these um
52:37
encouraging stories from our long term survivors um
52:42
which are um you know
52:43
giving all of us hope
52:44
and also helping us figure out what helps some uh
52:48
patients live longer um
52:50
and that may help us you know
52:52
design better studies in the future
52:54
um
52:56
there was one question in the chat
52:57
that I wanted to answer
52:59
they were asking if what about the patients
53:01
HLA-A0201 positive
53:04
and what about was like I think their question was like
53:06
can they have also PHP so um
53:09
again um
53:11
we know that most patients
53:13
need a combination of systemic
53:15
plus liver directed therapy
53:17
as you know Tebentafusp was approved as
53:20
a drug that can help in increase survival
53:23
and give survival benefit
53:25
so that can be used as systemic therapy
53:27
depending on the burden of the disease
53:30
um again
53:31
it's a multidisciplinary discussion with our colleagues
53:33
and um
53:35
sometimes we add liver directed therapies
53:37
different types PHP Y90
53:40
Immunoembolization sometimes
53:42
or radiation cryo ablation
53:45
different types
53:46
and depending on the size and location of the lesion um
53:49
and um we also
53:51
with the help of our colleagues from different centers
53:54
showed that there was benefit
53:55
in addition of liver directed therapy to Tebentafusp
54:00
so those are things that um
54:02
we need to basically um
54:05
think out of the box and be creative and um
54:08
help make the best treatment option for the patients
54:12
we've been doing that too Kam
54:13
we've been had
54:15
um Bartosz and I have had several patients on Tebentafusp
54:17
and PHP um
54:20
from what I can remember like
54:21
they're all everyone's doing super well um
54:24
like dramatic
54:26
again these are anecdotes
54:27
so I don't wanna you know
54:28
generalize it to 100 people
54:29
but like I'm
54:31
I've seen dramatic results like
54:33
like crazy results um
54:35
I would love to see a trial on this um
54:38
even if it's a single arm
54:39
you know combo trial of Tebentafusp plus PHP
54:43
uh I would love to
54:44
to see something like that
54:45
make it simple clean straightforward
54:47
you don't even have to randomize patients
54:48
just enroll you know
54:49
75 people I think that could be done
54:51
so we can at least you know
54:53
in a systematic way
54:55
show what the response rates and the
54:57
and the survival is definitely yeah
54:59
you I point out a good um
55:02
basically point that we
55:04
definitely need to do it in the right way
55:07
and um
55:08
the reason for clinical trials is that we have to show
55:11
scientifically what exactly works
55:13
instead of you know
55:14
a few anecdotes from each absolutely
55:17
um so I do want to kind of tap into a little bit of um
55:22
just kind of
55:22
how we can use the Chopin protocol in practice
55:25
I know that all three of you have seen it used
55:27
and have utilized this kind of protocol in practice
55:30
um but what room is there for personalization
55:32
because like
55:33
I know doctor
55:35
Chmielowski you the
55:36
you mentioned that there's
55:38
you know a lot of
55:39
a lot of concern from patients around
55:41
oh like
55:41
I don't want to use that IPI
55:42
you know Ipi Nivo
55:43
that has really really bad side effects
55:44
like you know it
55:46
there's a lot of scare around the use of
55:49
what looks like historically
55:50
has been a pretty ineffective immunotherapy
55:53
right at least for uveal melanoma
55:55
just on its own so um
55:58
do you see patients you know
55:59
coming to you that that have those kinds of concerns
56:01
and how do you address those
56:02
like kind of in practice
56:04
um I guess this is maybe more of a
56:06
a medical oncology specific question
56:08
we always respect concerns
56:10
we try to reassure
56:11
not everybody has terrible side effects
56:14
and if the people have side effects
56:16
we know how to manage them
56:18
and we can help them to manage the side effects
56:21
and be with them we do have quite an uh
56:25
dangerous disease so if uh
56:28
I always say you know
56:30
let's be as aggressive as we can
56:32
because the pay off might be the best
56:34
you know but uh
56:36
but we in
56:38
but of course you know
56:39
we respect concerns and this
56:41
try to explain and take through and
56:46
yeah absolutely
56:48
um so if a patient comes to you and says OK
56:50
like I see the Chopin results
56:52
they say that we're using a lower dose of ipilimumab
56:55
and kind of the the normal volume of nivolumab
56:57
um so I guess my understanding
56:59
this is the Chopin results
57:01
used kind of a modified version of the dose of
57:03
Ipi Nivo to start um
57:06
if I as the patient
57:07
want to say try something different
57:09
I wanted to try maybe I
57:11
I've heard about Opdualag or I've heard about
57:14
you know
57:14
just something else that is an immunotherapy that
57:17
you know might have some level of potential
57:19
like what level of
57:20
of discussion do you guys have with patients
57:23
or
57:23
have you ever had a patient who comes to you and says
57:25
yeah I don't want to do Ipi Nivo or I can't
57:27
maybe they've tried it before
57:28
and
57:29
they've had really poor side effects from it already
57:31
um how do you guys address that
57:34
Kam do you want this I was hoping you would go first
57:38
ha ha ha
57:39
yeah and
57:40
and that's a great question Danet
57:42
um and I think Bartosz and I probably both have had uh
57:46
these situations that
57:47
probably because of concern for toxicity
57:51
or prior toxicities and maybe a rechallenge um
57:55
and there is worry that you know
57:56
Ipi Nivo may not be the safe choice for the patients
58:00
um so in reality
58:01
we have some data that um
58:04
as you know the responses to single agent immunotherapy
58:07
are much lower um
58:10
so there there is that challenge
58:12
that you're exposing someone to a drug
58:15
that has a low chance of working
58:17
and higher chance of toxicity
58:19
but there is also this other combination of um
58:22
nivolumab and relatlimab
58:23
that hasn't been tested in combination with PHP
58:26
um in general
58:28
we tend to do something that there is some data on it
58:32
instead of just mixing like cooking in the kitchen
58:35
but sometimes we end up doing that because uh
58:39
we see that there is some need for systemic therapy
58:42
for the disease that's growing outside the liver
58:44
and if Ipi Nivo is not the safe option
58:46
maybe we can go for another option called Nivolero
58:50
or sometimes Ipi Nivo was tested before
58:52
and there was disease progression
58:54
so we use this other combination
58:56
to see if there are some chances again
58:58
there's not a lot of data
59:00
but there were some cases that had some responses
59:03
with the second combination um
59:06
after Ipi Nivo we know cutaneous melanoma
59:09
the chances are lower that
59:11
after
59:12
there is failure to one immunotherapy combination
59:15
to use the second one but again
59:17
that's something that needs uh
59:20
to be discussed uh
59:21
particular for each patient
59:23
and sometimes there are success stories
59:25
so um
59:26
it at the end is um you know
59:29
up to the patient and the oncologist
59:32
as a team to make that decision uh
59:35
in a situation that there is a rare disease
59:37
with few treatment options
59:40
to add to just one sentence
59:41
you know so one thing
59:43
which we know I do
59:44
which we know I know
59:45
I do not generally recommend Opdualag
59:48
as a first line treatment to know
59:51
so if it is there
59:53
we have some already data in uveal melanoma
59:56
coming it from Florida
59:58
is that it does not appear as Opdualag alone
1:00:02
as a first line treatment
1:00:03
is much better than a single agent nivolumab
1:00:08
but if somebody already had nivolumab ipilimumab
1:00:11
if they had this other treatments this
1:00:14
I'm not saying oh
1:00:16
you shouldn't use Opdualagat all
1:00:18
but if you try to use a first line treatment
1:00:20
probably it's not the best choice
1:00:23
I'm the patient who told my doctor
1:00:25
we're doing this instead
1:00:27
no it's okay
1:00:27
you're not I said I don't like I
1:00:29
I had too many too many personal issues with the
1:00:33
the possible side effects
1:00:34
that could affect my day to day life
1:00:35
as a 34 year old woman um
1:00:38
with Ipi Nivoand I said I would
1:00:40
you know if we're gonna try an
1:00:41
an immunotherapy I wanna push for one
1:00:43
that has a lower side effect profile
1:00:45
um it ended up
1:00:46
at least in my case probably being the right choice
1:00:48
because I developed a grade 4 side effect from Opdualag
1:00:52
that I probably would have even more likely
1:00:54
developed with Ipi Nivo
1:00:55
so anyway there's just
1:00:57
there's so much room for personalization here
1:00:59
and I think that what I hope that we
1:01:01
as patients can take away from this
1:01:03
is that
1:01:04
because we have the Chopin data to fall back on
1:01:07
that's why we can kind of personalize this
1:01:09
why we can piece out okay
1:01:11
maybe we try this instead why
1:01:12
you know
1:01:12
we can fit the pieces of the puzzle together with
1:01:15
you know the border of the puzzles already been made
1:01:17
if that makes sense
1:01:19
one more sentence you know
1:01:21
since you mentioned side effects
1:01:22
that you develop side effects on immunotherapy
1:01:24
when you are doing your combination treatment
1:01:27
this is a natural concern for the patient
1:01:29
so oh
1:01:29
my god you know
1:01:30
I was supposed to do this cycle
1:01:32
then PHP then another and another
1:01:34
and suddenly I have a side effects
1:01:36
and they have to put my immunotherapy on hold
1:01:39
and this so
1:01:40
so I'm right now not following the protocol
1:01:42
so I'm completely you know it's
1:01:44
it's a disaster
1:01:46
and we have to say you know
1:01:48
when what we want from our drugs
1:01:51
from our immunotherapy
1:01:52
is not necessarily how many doses you receive
1:01:54
but how active your immune system is
1:01:58
because it's not the drug that's doing the job
1:02:00
it's the immune system that's doing the job
1:02:02
so if you develop side effects
1:02:04
it means when your system might be
1:02:05
immune system is in hyper mode
1:02:07
and that's why it's giving you side effects
1:02:09
you may not need the next dose
1:02:11
you know
1:02:12
and so I would say don't get discouraged
1:02:15
if you develop side effects and you have
1:02:17
and your treatments are delayed or something
1:02:20
this this doesn't
1:02:21
not necessarily mean when it's not gonna work
1:02:23
yeah um
1:02:24
that is actually one of the questions we had to kind of
1:02:26
to expand on that is um
1:02:29
where did it go side effects um
1:02:33
how often or
1:02:34
or I guess specifically with this combination approach
1:02:38
Doctor Padia
1:02:39
where can patients you know
1:02:40
best read the information around the study
1:02:42
or is it not published available yet
1:02:45
um so we have questions about like how
1:02:47
you know how the side effects looked
1:02:49
for the group of patients in the study
1:02:51
yeah so great question
1:02:52
um I have the same question
1:02:53
in fact because the
1:02:55
the study was presented at a medical conference
1:02:58
in November 2025 it is currently what's called in press
1:03:03
meaning it is about to be published in
1:03:05
I think what's called The Lancet Oncology
1:03:08
um and I uh
1:03:09
last I heard
1:03:10
it will be published in the first week of March
1:03:14
so uh
1:03:15
you can hopefully download it
1:03:17
you know it again
1:03:18
it's gonna be medical jargon uh
1:03:20
that's how all scientific publications are
1:03:22
but it should be out in March
1:03:24
and I'm actually you know
1:03:25
I don't know I was not an investigator on the trial
1:03:27
I'm looking forward to the details as well
1:03:29
um you can always I
1:03:31
I'm sure you can Google it
1:03:33
if you Google like
1:03:34
uveal melanoma and Chopin you can get summary stuff
1:03:38
like summary slides and even
1:03:39
most of the slides I did are open access slides
1:03:42
um you can
1:03:43
you can get the kind of
1:03:45
the basics of the trial and the trial results that way
1:03:48
as well and also um
1:03:51
you can you know
1:03:52
honestly
1:03:52
feel free to just email the primary investigator
1:03:55
uh uh
1:03:56
who is the lead investigator
1:03:58
and I've met them they're super nice
1:04:00
Mark Burgmans is the IR um
1:04:02
and uh uh
1:04:05
Ellen Kapiteijn is is the medical oncologist
1:04:08
they're wonderful people
1:04:09
you could probably just email them and say hey
1:04:11
can I get a summary and they'll send it to you
1:04:13
hmm no
1:04:13
I love that that's so cool
1:04:14
I didn't know you could do that
1:04:15
yeah I was just gonna point out
1:04:17
the trial has become so popular that when you Google
1:04:21
first it says Chopin melanoma
1:04:22
then it's Frederic Chopin
1:04:25
the musician
1:04:26
there you go then first
1:04:28
but oh
1:04:29
ask your medical
1:04:31
ask your medical oncologist also
1:04:33
you know they also know they are aware of data
1:04:35
this they can look up
1:04:36
and they might not have been a part of a clinical trial
1:04:39
but they can guide you
1:04:41
and this answers one of our other questions
1:04:43
from one of the attendees
1:04:44
they were asking you know
1:04:45
is the Chopin protocol
1:04:46
widely known by treating oncologists yet
1:04:48
given that the trial results are not published
1:04:50
so what I'm hearing is
1:04:51
you guys are seeing it noised about
1:04:52
far more in the last couple of months
1:04:55
um is that
1:04:56
is that feeling pretty accurate
1:04:57
do you think it's getting more noise
1:04:59
it is correct you know
1:05:01
but I have to say we are a little bit biased
1:05:03
because we are in a small group of
1:05:05
of medical oncologists who are melanoma oncologists
1:05:09
who have also interest in uveal melanoma
1:05:11
not only skin melanoma so this group
1:05:14
so if you have a general oncologist
1:05:16
in smaller practice of this
1:05:18
they may not be fully aware
1:05:20
you know so the patient
1:05:21
but the patient can make them aware
1:05:23
and then they will start digging into it
1:05:25
you know but absolutely yeah
1:05:26
I think there are centers of excellence
1:05:28
in each part of the United States
1:05:30
at least that um
1:05:32
the there is this multidisciplinary group designed for
1:05:37
um delivering PHP to the patients
1:05:40
including interventional radiologists who um
1:05:43
lead um
1:05:43
the treatment their perfusionist um
1:05:46
you know techs um
1:05:47
cardio um
1:05:49
anesthesiologists um
1:05:50
surgeons who admit the patient
1:05:52
high level care uh
1:05:54
units uh
1:05:55
to take care of the patient overnight
1:05:57
and then us medical oncologists that work together
1:06:00
so um
1:06:00
one thing is to you know
1:06:02
know which centers are available close to you
1:06:06
just like a Doctor Padia we have been doing this
1:06:09
and Doctor Chmielowski doing this
1:06:11
on the Upper East Side of the states and Massachusetts
1:06:17
and so yes
1:06:19
maybe other oncologists
1:06:21
that are not focusing on uveal melanoma
1:06:25
are not fully aware of this
1:06:27
but it's um
1:06:28
you know patients um
1:06:29
like yourself who are devoting their life and career
1:06:33
to make others aware that's very helpful
1:06:35
so that the patients can um
1:06:38
you know actively seek for novel treatments
1:06:41
I was gonna also just add
1:06:42
if you're not aware
1:06:43
in the back end of our zoom event here
1:06:45
and also just I'll just say it out loud um
1:06:47
Hepzato Access and hepzatokit.com
1:06:50
those are some really unique resources
1:06:52
where you can go as a patient or as a caregiver um
1:06:55
and even other practitioners
1:06:56
you know we can
1:06:57
we can search
1:06:57
and we can find their currently open sites
1:07:00
um they're really good at
1:07:01
at updating the most recently updated our uh
1:07:05
most recently opened sites
1:07:06
so for example
1:07:07
I think the most recent site that just opened
1:07:09
is actually in Texas um
1:07:11
in Dallas Texas
1:07:12
I think at MD Anderson there
1:07:14
and so those updates to which sites are open
1:07:17
those are actively being you know
1:07:18
put up online on Hepzato Access
1:07:21
Hepzatoaccess.com and Hepzatokit.com
1:07:24
both of which are resources
1:07:25
US patients can go into the back end of this event um
1:07:28
even after we conclude the event
1:07:29
and you can access those links
1:07:31
um they've got a map
1:07:32
like you can just search it
1:07:34
um oh OK
1:07:35
I got I got an update that
1:07:37
OHSU in Portland is the most recent site
1:07:40
so like
1:07:40
these sites are opening rapidly
1:07:42
I mean they
1:07:43
they have really picked up some good momentum
1:07:45
um I know we've got Dallas
1:07:47
we've got Portland we've also got
1:07:48
I just had heard about Utah like um
1:07:51
Utah has a site
1:07:52
and they are also utilizing the Chopin protocol
1:07:55
and so I mean
1:07:56
there are definitely doctors out there
1:07:58
who are aware of this
1:07:59
it's just a matter of maybe finding them
1:08:01
and I think sometimes as patients
1:08:03
we have to be willing to step outside the box of oh
1:08:05
I'm most comfortable with this doctor
1:08:07
or I've been told that
1:08:08
this is the only doctor I should see
1:08:10
but what about maybe going outside the box
1:08:12
and getting a second opinion
1:08:14
you know like there's
1:08:14
there's definitely room for that for sure
1:08:16
um so
1:08:17
Doctor Padia you mentioned
1:08:18
you average about four to six procedures per month
1:08:21
is that meeting the total demand of like
1:08:23
patients you have who want Hepzato
1:08:24
or do you have like
1:08:25
kind of a backlog and you have to turn patients away
1:08:28
no we don't necessarily have a backlog
1:08:30
we would have a backlog but what we're doing
1:08:32
as was mentioned
1:08:32
is that more and more sites are coming on board
1:08:35
so our referral base
1:08:38
a year and a half ago
1:08:39
was basically the entire Pacific time zone
1:08:41
and mountain time zone like
1:08:42
basically
1:08:43
everyone in the western half of the United States
1:08:44
was flying into UCLA to get this done
1:08:47
we've been the company and
1:08:49
you know we've been part of it
1:08:50
to train other sites for example
1:08:52
um Salt Lake City in Utah is now doing it
1:08:54
and UC San Diego is doing it
1:08:56
and Cedar Sinai and excuse me
1:08:58
city of hope in Los Angeles is doing it
1:08:59
so that's helped uh
1:09:01
because I think if that didn't happen
1:09:03
and then the Chopin stuff comes out
1:09:04
then I don't want to be backlogged
1:09:06
because I don't want to delay patients getting care
1:09:08
I would rather have them go locally
1:09:10
if they can get it done in a good way
1:09:12
and get it done by caring physicians
1:09:14
who are technically skilled um
1:09:17
so we're probably um
1:09:19
we're like just for us
1:09:21
we're like full for February and March
1:09:24
I think we have opening spot
1:09:25
so we're
1:09:25
we're pretty much like riding the wave right now
1:09:27
I think if we have more patience
1:09:29
we may start to get backlogged and
1:09:31
you know so
1:09:31
and one of the challenges from a logistic point of view
1:09:35
is that we we reserve a lot of room time for this um
1:09:38
in in the hospital
1:09:39
and you know
1:09:40
there's a four hour block
1:09:42
we have to get certain anesthesiologists for it
1:09:44
we have to uh
1:09:45
there's we have 18 interventional radiologists at UCLA
1:09:48
there's two of us who do this
1:09:49
and I do most of them so
1:09:50
you know every
1:09:51
all the
1:09:52
kind of stars have to align for us to find a spot
1:09:55
and that's why we we do a certain number per month
1:09:59
gotcha okay
1:10:00
I think that makes sense um
1:10:03
uh let's see
1:10:04
how frequently would you guys expect a patient to need
1:10:07
um
1:10:09
need the treatment so I'm gonna
1:10:10
I'm gonna assume this question is
1:10:11
is asking how frequently would you expect a patient
1:10:13
to need the treatment
1:10:14
kind of outlined in the Chopin protocol uh
1:10:17
for a long term intervention
1:10:19
and I think maybe the general first
1:10:21
first answer to that question is
1:10:22
we don't know we don't know yet
1:10:24
because the Chopin trial only covered two PHPs
1:10:28
and was it three
1:10:30
Ipilimumab and Nivolumab 4 4 it was four
1:10:33
as Doctor Doctor Montazeri says um
1:10:36
so do you guys do you guys have a
1:10:38
a theory have you seen anything
1:10:39
in your own clinical practice
1:10:40
of utilizing this protocol
1:10:42
one thing
1:10:43
which we don't even know
1:10:45
in the original development of PHP
1:10:47
was that people are getting six procedures
1:10:50
we don't know you know
1:10:51
we do two and then we here at UCLA
1:10:55
we usually take a break a little bit
1:10:57
you know and say OK
1:10:58
let's see what happens because
1:11:00
we had patients that didn't need the third procedure
1:11:03
for a year or something after the original
1:11:06
so do we need to stack them up front
1:11:08
you know so the approach which we use
1:11:12
we kind of adjust to what we see on the scan
1:11:16
you know if we see that there might be active disease
1:11:19
or worsening disease then we do again to
1:11:22
but we don't necessarily do six upfront
1:11:25
you know is it the better approach or worse
1:11:27
we don't know that you know
1:11:28
this are very good questions
1:11:30
you know but uh uh
1:11:33
but we try to space them out
1:11:35
there's a lot of debate in the IR community about this
1:11:37
we we've had
1:11:38
you know meetings internal
1:11:40
like with me and 15 other interventional radiologists
1:11:42
and we kind of all disagree on this
1:11:45
uh I think I'm right
1:11:46
they think they're right you know
1:11:47
so people are like look
1:11:48
let's just offer four to six
1:11:49
all up front um
1:11:51
as Bartosz says we take a more patient approach uh
1:11:55
in terms of like
1:11:56
do we do two we restage
1:11:57
and then we make a decision um
1:12:00
you know and
1:12:00
and part of this is to get a little bit more long term
1:12:03
durability and longevity instead of rushing to do six
1:12:08
and the key thing I want to remind everybody
1:12:10
is that while these patient
1:12:12
these procedures are well tolerated
1:12:13
it does cause some fatigue for a few weeks um
1:12:16
it does cause some nausea for a few weeks
1:12:17
it can drop your white cell count
1:12:19
so it's not like it's you know
1:12:21
nothing and if you get
1:12:23
you know in my experience
1:12:23
if you get six right up front
1:12:25
it can it can wear you down a little bit
1:12:27
so I my personal preference
1:12:29
and again this is anecdotal
1:12:32
is to space them out a little bit
1:12:34
as Bartosz said
1:12:35
what are you seeing in practice
1:12:36
I'm Doctor Montazeri well um
1:12:39
so the way the focus trial was designed
1:12:41
it was like six to eight weeks
1:12:43
and sometimes in some patients
1:12:45
we do more closely depending on the disease burden
1:12:47
again yeah
1:12:48
we we may make different decisions
1:12:51
based on how much disease we see
1:12:53
based on um
1:12:54
how you know
1:12:55
physically um
1:12:56
a patient is doing and how strong they are
1:12:59
it's technically
1:13:01
Doctor Padia is the best person to comment on that
1:13:03
than the rest of us here or actually
1:13:05
Danet you're the best person to comment on it
1:13:07
but as they describe it it's like running a Marathon
1:13:11
so it's a lot of burden on your cardiovascular system
1:13:14
um yeah
1:13:15
it's a it's not like a walk in the park
1:13:17
but sometimes when you worry that
1:13:19
you know and there is a lot of disease
1:13:21
and you have to continue the treatment
1:13:23
and we do back to back treatments um
1:13:27
as we have been saying it during this whole hour
1:13:31
hour and a half is that we really don't know whether
1:13:35
unless we compare them head to head
1:13:37
so there needs to be clinical trials
1:13:39
comparing more PHPs versus um
1:13:43
fewer PHPs and that may be also difficult depending on
1:13:46
you know how similar the patients on each arm are
1:13:50
yeah so to be determined
1:13:53
we're still figuring it out as we go patient to patient
1:13:55
um I think what I hear kind of
1:13:59
from patients in the community
1:14:00
who have had the PHP treatment who've
1:14:02
you know continued having Hepzato to some degree
1:14:04
is that generally
1:14:05
I think a lot of doctors are following at least a okay
1:14:08
we do two then we check and we see what's happening
1:14:12
and then we make a decision for the next two
1:14:14
and we kind of just graduate from there um
1:14:16
with the you know
1:14:17
kind of end goal in mind of we hit six
1:14:19
and when that's when if we hit six consecutively
1:14:22
then we gotta take a solid break of some kind um
1:14:25
just to give you know
1:14:26
give the body a break
1:14:26
give the immune system and all of it
1:14:28
give it a break uh
1:14:29
having had five upcoming on six
1:14:31
like I can say I'm excited to get a break
1:14:33
I'm excited to get a break
1:14:35
um one of the things that we had a question come in
1:14:39
that is kind of back to our trial discussion was and
1:14:42
and I think this will actually help
1:14:44
maybe just
1:14:45
define a little more
1:14:46
about the different types of clinical trials
1:14:48
um
1:14:49
this person says it seems if I choose a clinical trial
1:14:51
there's still a fifty
1:14:52
fifty chance that I end up only on the control arm
1:14:54
not the experimental drug
1:14:56
and if you wait too long
1:14:57
your liver is more than 50% affected
1:14:59
then you might become ineligible for PHP
1:15:01
so I guess there's kind of two parts to this question
1:15:03
that I think we should address
1:15:04
one is are all clinical trials like that
1:15:07
because I I know the answer
1:15:08
but I want you guys to give the answer
1:15:10
so not all clinical trials are randomized
1:15:13
you know more advanced clinical trials
1:15:15
than may lead to the approval of a therapy
1:15:18
when usually they are randomized
1:15:19
and they are compared to standard of care
1:15:22
any I I
1:15:25
you know I
1:15:26
we talk
1:15:26
I talk about clinical trials to my patients probably every day
1:15:30
and the options and why clinical trials is an option
1:15:34
and very often there is a standard arm
1:15:36
as a control arm
1:15:38
I when we design these trials
1:15:42
you know we design
1:15:43
or they are designed
1:15:44
and they are reviewed by ethics committees
1:15:47
and scientific committees
1:15:49
if there is a randomization
1:15:52
it means when there is a question
1:15:54
when we don't know if a new
1:15:56
a new therapy is actually better than the old therapy
1:16:00
of course we are excited about new therapies
1:16:02
that's why we pursue this clinical trials
1:16:05
but if we knew when the new is better than the old
1:16:08
we would never randomize patients
1:16:10
you know so what it means
1:16:12
if you get randomized to the control arm
1:16:14
it does not mean that you are a loser
1:16:16
then you oh
1:16:17
my god I got bad luck
1:16:19
you might be getting actually
1:16:21
a better therapy than whatever new is coming
1:16:23
you know so um
1:16:27
so I would not say I would not discourage people say
1:16:30
okay I'm on a worse arm
1:16:32
there is of course
1:16:33
the concern if the disease progresses
1:16:35
and this will I be an a candidate for
1:16:38
for a Hepzato later but what happens is this
1:16:43
patients are usually on clinical trials
1:16:45
followed quite closely
1:16:46
so anytime we see worsening of the disease
1:16:49
we start we take the patient off the clinical trial
1:16:52
and switch them to whatever we
1:16:54
we think is appropriate okay
1:16:57
um I don't wanna spend too much time on this question
1:16:59
so unless somebody's like
1:17:00
itching to to dive in and weigh in
1:17:03
I wanna move to the the next one
1:17:05
which I think we actually already answered this one
1:17:07
Doctor Montazeri did you
1:17:09
you covered the one about like the
1:17:10
the different class like
1:17:12
class one prime positive question at the bottom right
1:17:15
no I didn't see that sorry
1:17:16
would you please okay
1:17:17
so I guess this is really pretty
1:17:18
a pretty general question um
1:17:21
I think there and
1:17:22
and whoever whoever this was please
1:17:24
you know clarify your question if you need to
1:17:26
but based on you know
1:17:27
some of the things that I had discussed earlier
1:17:30
is PHP the Chopin protocol
1:17:32
is this something that is available to someone who is
1:17:34
prame positive
1:17:35
class 1 um
1:17:36
who ends up metastasizing
1:17:39
yes so um
1:17:40
it was not um
1:17:42
basically um
1:17:44
it's it's not um
1:17:47
selective or um
1:17:48
randomized based on the prame status or HLA status
1:17:52
um and again um
1:17:54
what we are doing is not
1:17:55
within a clinical trial setting uh
1:17:58
it's basically extrapolating data
1:18:00
from that clinical trial
1:18:02
that was a positive and encouraging trial
1:18:04
and using it in practice um
1:18:06
so depending on what you have been treated uh
1:18:10
with in the past
1:18:11
we may decide to add immunotherapy to the PHP treatment
1:18:14
if that's the right approach
1:18:16
but a prame positivity doesn't change that
1:18:19
or GEP class
1:18:21
gene expression profiling class
1:18:23
wouldn't change that decision
1:18:25
okay just one more sentence
1:18:27
since I'm itching is because
1:18:29
you know very often right now
1:18:30
patients come and say oh I put in this AI engine
1:18:35
and the information and they told me
1:18:37
I have to ask you what am I
1:18:39
class 1 class 2
1:18:40
am I prame positive prame negative
1:18:42
and it's an important question
1:18:44
but it's an important question
1:18:45
for people who did not develop metastases
1:18:48
because this predicts the risk of developing metastases
1:18:52
once you have metastasis
1:18:54
this information is not important anymore
1:18:56
you know because you already
1:18:58
so even if you were class 1 prame negative
1:19:01
the best prognosis if you develop metastasis
1:19:04
you were in this unlucky ones who did develop
1:19:07
so yeah
1:19:08
no that's a good point
1:19:09
uh okay
1:19:10
how about you guys um
1:19:12
Doctor Montazeri
1:19:13
how long have you guys been doing PHP at your center
1:19:16
like have you had any patients
1:19:17
receive more than six treatments
1:19:19
and this is for all of you
1:19:19
um yeah
1:19:21
so we have been doing pretty much about two years
1:19:23
we have now treat and we have now given about 90 PHPs
1:19:28
36 patients or more
1:19:31
maybe that was the latest data that I had
1:19:34
um we have been giving about four cycles
1:19:39
sometimes the um
1:19:40
but I think the average is four cycles
1:19:42
that we have been giving to some patients
1:19:44
we have been giving six cycles of PHP so far
1:19:46
I don't think we have um
1:19:49
done beyond six treatments
1:19:54
it may you know
1:19:55
in the future change if there is like
1:19:58
a big time lapse between the 6 treatment
1:20:00
and if we want to try that again
1:20:03
but I don't know if my colleagues at other centers
1:20:06
have had yeah
1:20:07
I mean I think part of it Danet
1:20:08
is that you know
1:20:09
as Kam said
1:20:10
this has been available commercially for two years
1:20:13
so I think if you ask that question again to us
1:20:15
in a year from now we may have a different answer
1:20:17
but I have not had any patients more than six
1:20:20
that being said
1:20:21
I'm not really opposed to doing more than six
1:20:24
as long as they've tolerated the six before
1:20:27
and I as long as we think that there is benefit
1:20:30
more than risk we always do this
1:20:33
anything you get like medications or procedure
1:20:35
we do a risk benefit analysis
1:20:37
and we find um
1:20:39
look at I think after 6
1:20:41
maybe your risk benefit ratio may change a little bit
1:20:43
compared to procedure number one
1:20:45
so we have to discuss that um
1:20:47
and we have to we have to weigh that in um
1:20:50
so it's not necessarily a straightforward yes
1:20:53
you can do more than six or no
1:20:54
you can't because it's gonna be uh
1:20:56
as we kind of said the whole hour
1:20:58
it has to be individualized
1:21:00
yeah um
1:21:00
I suspect we will end up doing more than six
1:21:03
on certain patients in the future
1:21:05
we just haven't yet
1:21:06
but that's also because we started two years ago
1:21:08
just like MGH well and
1:21:10
and I I mean I'm
1:21:12
I'm not going to say exactly where
1:21:14
but I can tell you that
1:21:15
I have spoken to patients who are in Europe
1:21:17
who are saying that in Europe
1:21:18
they are doing more yeah
1:21:20
so there is definitely hope that
1:21:21
that could happen in the future
1:21:22
just here in the States
1:21:23
we haven't quite gotten there yet
1:21:25
because we haven't had it here available long enough
1:21:27
is what I'm hearing um
1:21:29
as a patient about to complete six
1:21:31
who happens to have tolerated it really well
1:21:33
I'm in the camp of I volunteer as tribute
1:21:35
like I will volunteer to do it again
1:21:38
you know six months from now
1:21:39
if we think that there's the potential
1:21:41
that this could keep me cancer free for even longer
1:21:44
but I happen to be one of the patients
1:21:46
who tolerates it insanely well
1:21:48
you know insanely well compared to other patients
1:21:51
maybe that's because I'm younger
1:21:52
maybe it's I mean
1:21:53
who knows but
1:21:56
but I think that you know that's
1:21:57
that's one of the big reasons for this discussion
1:21:59
right is that this is something we
1:22:00
we hope we can see some personalization for patients
1:22:03
and you know
1:22:04
as patients you guys can be your best advocates
1:22:06
um
1:22:08
and if you're like me
1:22:09
and you think that you tolerate it really well
1:22:10
then then ask like
1:22:12
what's it gonna hurt the worst they can say is nope
1:22:14
not yet here's why yeah absolutely
1:22:18
okay um
1:22:19
well I think to wrap um
1:22:21
I want to just have us you know
1:22:23
wrap up like
1:22:24
maybe one important message
1:22:25
that patients who've listened in on this webinar
1:22:27
could take away uh
1:22:28
from learning about the Chopin data and the study
1:22:31
when they're making treatment decisions
1:22:33
with their care team whether they're newly metastatic
1:22:36
or somewhere in the middle
1:22:37
you know somewhere in the mix
1:22:38
I just want to repeat what I said
1:22:40
you know
1:22:42
be optimistic you know
1:22:44
you can see from this data
1:22:45
when we are making a difference
1:22:47
and patients live longer and so have hope
1:22:52
yeah absolutely
1:22:53
Doctor Montazeri yes
1:22:56
hope always helps um
1:22:59
if today is the day for hope and love
1:23:01
and I hope that's every day
1:23:03
um and I wanna thank your
1:23:06
thank your audience for you know
1:23:08
spending um
1:23:09
their Valentine's Day with us
1:23:11
I hope this um
1:23:13
conversation has helped them
1:23:15
um it's a definitely a better
1:23:18
not never
1:23:19
there is never a good time to have this disease
1:23:21
but definitely now it's better than 10 years ago
1:23:24
or even a shorter
1:23:25
so be hopeful and be on the lookout for new treatments
1:23:30
absolutely um
1:23:31
Doctor Padia yeah
1:23:32
that I just want to echo my colleagues and um
1:23:35
you know I'm
1:23:35
I'm relatively now optimistic um
1:23:39
and I'm a I'll be honest
1:23:40
I'm a glass half empty type of guy
1:23:42
so I I think that these
1:23:44
you know some of the data has been super promising and
1:23:47
um we were seeing fantastic results in most patients
1:23:51
so I would say you know
1:23:53
to encourage you guys to not everybody to not give up
1:23:55
and it's nice to see you know
1:23:58
we're starting to
1:23:59
it used to be like trials were kind of inching
1:24:01
and now we kind of seeing big leaps
1:24:03
so I hope that not just this
1:24:05
but other trials
1:24:06
both in the medical oncology space and the IR space
1:24:08
you know continue to build on that
1:24:10
so I think that you know
1:24:11
we're gonna start to in the next three to four years
1:24:13
we're gonna start to see really
1:24:14
kind of interesting
1:24:15
and new developments in the uveal melanoma space
1:24:19
to get people better and better results
1:24:23
yeah no I
1:24:24
I mean I love everything
1:24:25
that all of you guys have talked about today
1:24:27
I really appreciate um
1:24:28
all of our participants on the webinar questions um
1:24:31
people sending in you know
1:24:32
their feedback and their two cents in the chat
1:24:34
all of you guys who just like Doctor Montazeri said
1:24:37
spent your Valentine's Day here with us
1:24:38
um we could not have these kinds of discussions
1:24:41
without patients participating
1:24:43
um it really does help
1:24:44
so thank you guys for participating
1:24:45
and just being your own best advocates
1:24:47
and being here to learn um
1:24:49
I do want to give just a brief disclaimer
1:24:51
that nothing that we shared here
1:24:52
should be taken as explicit
1:24:54
individual medical advice um
1:24:56
I am you know
1:24:57
I'm a patient I'm not an expert
1:24:58
these doctors are experts in their fields
1:25:01
and they are sharing but nothing no
1:25:03
none of them are well
1:25:04
actually a few of you said that your doctor was on here
1:25:07
but for the most part this might not be your doctor
1:25:09
so make sure you take this information
1:25:11
what you've learned take these questions maybe
1:25:13
that you have um
1:25:14
or take the information to your doctor and just say
1:25:16
look I like this
1:25:17
can we talk about it um
1:25:19
get the conversation going
1:25:20
especially if you have an oncologist
1:25:21
who maybe hasn't heard of the
1:25:23
Chopin data and let's just open up the conversation
1:25:25
I think that
1:25:26
that's really the best thing that we can have
1:25:28
as patients is doctors willing to have the conversation
1:25:30
um and
1:25:31
and doctors willing to like
1:25:32
let us drive our care so um
1:25:34
I want to just thank these three physicians for being
1:25:36
um being a huge part of that kind of a conversation
1:25:38
and just seeking to really individualize care
1:25:41
patient to patient um
1:25:43
obviously research and experience
1:25:44
you know anecdotally and in a research setting
1:25:47
helps to guide those decisions
1:25:48
but um
1:25:49
thank you guys for just showing that
1:25:51
you know patient preferences matter
1:25:52
and that you guys have you know
1:25:53
the goal of
1:25:54
of helping patients live their absolute best life
1:25:56
even when they're dealing with metastatic disease
1:25:59
thank you yeah absolutely
1:26:01
thanks so much guys
1:26:02
alright well
1:26:03
as we close out
1:26:04
I want to just say a huge thanks again to our um
1:26:07
our sponsors for the webinar series
1:26:09
we could not have done this without them
1:26:11
so thank you again for being here
1:26:12
you guys thanks for our sponsors
1:26:14
and we will see you guys next time
1:26:16
I was gonna tease this earlier and I forgot to
1:26:19
but I will just tease it now
1:26:21
that our next topic
1:26:22
is going to be covering more about CT DNA
1:26:26
which actually has some really good information
1:26:29
coming out soon um
1:26:30
in the Hepzato space as well around CT DNA
1:26:33
so we're getting really
1:26:35
really excited for that next webinar
1:26:36
be on the lookout on the newsletter
1:26:37
for both the study results
1:26:39
as we get those when they get published
1:26:41
like Doctor Padia said um
1:26:42
A Cure In Sights newsletter
1:26:44
we will put that out in our newsletter
1:26:45
as quickly as we can and on our social media
1:26:47
so thanks you guys for being here
1:26:49
make sure to subscribe and if you have the um
1:26:51
the wherewithal to you know
1:26:53
send a send a donation in
1:26:54
or send a donation form to your friends and family
1:26:57
to help us continue um
1:26:58
educating patients and having programs
1:27:00
that can aid patients in getting care
1:27:02
we would absolutely appreciate that
1:27:03
so thanks again for being here with us
1:27:05
and I will let you guys get back to your Saturday