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ESMO 2025 Highlights: Key Uveal Melanoma Trial Updates with Dr. Hadfield | The Eye Believe Podcast · The Eye Believe Podcast

• 0:03
  hey everybody
• 0:03
  welcome back to the Eye Believe Podcast
• 0:05
  today I'm joined with Doctor Matt Hadfield
• 0:08
  and he is at Providence Rhode Island
• 0:10
  and he's a medical oncologist
• 0:11
  if you haven't heard of him
• 0:12
  please check out the physician finder on
• 0:14
  ACureInSight.org
• 0:15
  you can find other doctors in your local areas
• 0:18
  and just kind of follow your zip code
• 0:20
  but we are gonna be chatting about major
• 0:22
  new uveal melanoma research updates
• 0:24
  and this is super helpful and important to patients
• 0:27
  because honestly
• 0:28
  like the ESMO studies that came out at the end of 2025
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  I think were probably some of the most hopeful studies
• 0:33
  that I have seen as a patient in like
• 0:36
  the five and a half years
• 0:36
  that I have been doing this podcast
• 0:38
  you know in addition to just the five and a half years
• 0:40
  I've been a uveal melanoma patient myself
• 0:42
  so tune in stay tuned for like
• 0:45
  the rest of the studies we're gonna reference
• 0:46
  but also please check that out on our website
• 0:49
  we'll link that in the show notes
• 0:50
  we kind of were talking before we started recording
• 0:52
  and Doctor Hadfield and I decided we were gonna chat
• 0:55
  briefly about something
• 0:56
  that's actually not in our list of ESMO studies
• 0:59
  there was an ASCO study on dietary fiber
• 1:01
  and immunotherapy that came out in
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  I think the summer of 2025
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  and Dr. Hadfield and I were just talking
• 1:06
  about how important this is
• 1:07
  and why more patients should know about it
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  so um
• 1:10
  Dr. Hadfield
• 1:10
  you wanna tell us a little more about that one
• 1:12
  yeah no
• 1:13
  thank you for having me and it was uh
• 1:15
  interesting
• 1:15
  as we were having kind of that sidebar conversation
• 1:17
  about your experience in clinic and
• 1:19
  and what
• 1:19
  uh you and your urologist
• 1:21
  uh have been speaking about
• 1:22
  and
• 1:22
  how high fiber diets
• 1:23
  have really entered the conversation
• 1:25
  and it's such an important thing to talk about
• 1:27
  so at ASCO 2025 the annual meeting
• 1:30
  there was the diet trial which was a randomized trial
• 1:32
  showing that a high fiber diet
• 1:33
  which was defined in the study as
• 1:35
  30 to 50 grams of fiber a day
• 1:37
  significantly improved response rates
• 1:39
  and survival for melanoma patients on immunotherapy
• 1:41
  so this this
• 1:41
  this study showed that those that had a high fiber diet
• 1:45
  had an objective rate of response of 77% versus 29% um
• 1:49
  and those not having a high fiber diet
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  and then the median event free survival uh
• 1:53
  was not reached in the high uh
• 1:55
  fiber arm um
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  versus 7.6 in the control arm
• 1:58
  so I mean
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  this is this is uh
• 2:00
  honestly one of the most um
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  you know when we think about practice changing studies
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  we we often think about those
• 2:06
  that have remarkable increases in efficacy um
• 2:10
  or or new therapeutic combinations that are
• 2:13
  are you know
• 2:14
  showing significant benefit
• 2:16
  but this is one of the most important
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  practice changing studies
• 2:19
  that's come out in the last year
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  given the the risk of having a high fiber diet is
• 2:24
  you know very
• 2:24
  very low um
• 2:26
  and uh the
• 2:27
  the benefit here is tremendous
• 2:29
  and I think it's important to highlight too um
• 2:32
  this study really stipulates and
• 2:34
  and and show that it's
• 2:36
  it's really the process of
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  or the the eating a high fiber diet
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  high fiber foods not necessarily fiber supplements
• 2:43
  because of
• 2:43
  the digestion of that high fiber food content
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  is really what's uh
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  recruiting these pro immunotherapeutic uh
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  microbiome uh
• 2:50
  organisms to to propagate that response
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  so um
• 2:54
  if you're a patient who is on immunotherapy um
• 2:56
  obviously this was in melanoma patients
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  but um I
• 2:59
  I think it's it's a it's
• 3:01
  it's a logical assumption that it
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  this is beneficial to anyone on immunotherapy
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  whether or not you have uveal melanoma
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  cutaneous melanoma or another malignancy
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  so definitely
• 3:09
  something that you should
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  speak to your oncologist about
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  cause it's very important
• 3:12
  yeah for sure
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  um and just from a
• 3:14
  you know personal note
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  I've been doing a high fiber diet
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  after Doctor Moser recommended that for me
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  in addition to my opdualag immunotherapy infusions
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  and I thought it was gonna be kind of hard
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  and then I actually was able to find a few
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  like good high fiber foods that are like
• 3:27
  good quality high quality
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  and they're not you know
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  they're not like a Metamucil supplement
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  like you mentioned like
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  so I am you know
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  like
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  I'm digesting the food versus um
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  taking a supplement
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  but another kind of like
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  little resource that might be out there for you
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  depending on your insurance
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  um I know there's various different like
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  nutritionist apps that you can join and that like um
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  that can be covered by insurance
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  I know for me like
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  I've been using the nourish app
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  and so I have a dietitian who actually
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  I can help like
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  kind of figure out okay
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  what foods are out there like
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  what could I use um
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  that are Whole Foods to like
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  bring that supplemental fiber into my
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  into my day
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  I just thought it was so fascinating and
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  and as somebody who really like
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  values the holistic stuff
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  like this was
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  this was a really neat study for me
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  and I was like say less or
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  you know
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  I will do it like that that's not a
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  that's not a hard thing for me to try
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  no it has
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  most definitely
• 4:17
  entered the conversation of every patient that I have
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  that is on immunotherapy or um
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  is starting immunotherapy
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  so it's it's
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  it's so good to I'm so glad you brought that up
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  because it's an important thing to touch on
• 4:27
  yeah for sure
• 4:28
  okay well
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  we'll make sure to link that ASCO study as well
• 4:31
  in our show notes and in the description
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  for those of you listening on our YouTube channel
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  which by the way
• 4:35
  thanks for being here thanks for subscribing
• 4:38
  but as we get into the rest of our conversation
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  can we just
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  cover a couple of things around kind of the phrases
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  the terminology in these studies
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  so that we know what patients are
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  so that patients listening at home like
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  kind of know what these mean
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  so I'm gonna give you like
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  just one at a time rapid fire
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  and we can just go through each of these
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  so can you define phase 1 versus phase 2 and phase 3
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  in a trial yeah
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  no absolutely
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  and and um
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  these are these are terms that can get very
• 5:04
  very overwhelming very very quickly
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  so it's a great thing to go through them
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  phase one studies are
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  by definition safety studies
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  and it's the first time a
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  drug is being used in patients
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  so these are
• 5:14
  these are drugs that have had years and years
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  and years of preclinical development
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  they've been studied extensively
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  and now we're at the point where
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  there are very promising therapies
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  that have made it to the clinic
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  but they're very small studies
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  they include just one arm of patients
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  and depending on the study
• 5:28
  they may be in one specific type of tumor type
• 5:31
  they may be in multiple tumor types
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  multiple solid tumor malignancies
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  or they may be in an enriched tumor type
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  meaning that there is a
• 5:39
  a biomarker that is being tested
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  and then we are studying
• 5:43
  if the patient has that biomarker on their tumor
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  if the drug works well in that patient population
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  um and then just quickly
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  phase 2 studies are
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  are typically slightly larger studies
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  where you're looking at something like a response rate
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  which we can talk about in a second
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  and it's limited to just one tumor type most often
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  and then phase 3 studies are really when you uh
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  you get into randomizing uh
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  to the new therapy versus an existing therapy
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  to determine which one is better
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  and you know
• 6:10
  in terms of the developmental process
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  phase 3 uh
• 6:14
  trials are the largest most robust uh
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  in terms of the statistics that go into them and
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  and that's the
• 6:19
  the trials that typically lead to them being approved
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  by the uh
• 6:22
  the regulatory bodies like the FDA
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  okay um
• 6:25
  you mentioned like
• 6:27
  smaller studies um
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  I know like
• 6:29
  some of the other terms that come up
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  are randomized versus single arm
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  so what's the difference between those two
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  right so um
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  when you have a a patient that is getting enrolled on a
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  a single arm study
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  that means when you sign the consent form
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  you talk to the the treating physician
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  you are being enrolled in one arm
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  meaning that there is just one therapeutic uh
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  intervention that you're getting
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  so
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  for instance uh
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  we're going to talk about the Immatics trial
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  that Doctor Sapna Patel presented at ESMO
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  and that was a single arm study
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  so those that got enrolled in the study
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  received that study drug there was no other
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  other intervention
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  a randomized study is when you enroll in the study
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  and then there is a a blinded randomization process
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  where you get enrolled to an experimental arm
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  which may include standard of care plus something else
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  this new experimental drug
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  or you get enrolled to standard of care
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  and that can be sometimes blinded or unblinded
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  so blinded would mean that you're enrolled to a group
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  and you don't know if you're getting the new study
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  drug or not and then unblinded as you do
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  but that's kind of the breakdown
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  phase 3 studies are randomized
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  phase 2 studies are sometimes randomized
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  sometimes not depending on the nature of the study
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  okay that makes sense
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  uh alright
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  we mentioned like overall survival
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  response rate things like that
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  what does response rate mean
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  and what about progression free survival
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  versus overall survival right
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  so um
• 7:49
  response rate is when we look at the
• 7:53
  the response of the tumor to the drug
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  so if if the
• 7:56
  if the tumor is staying the same or getting smaller
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  after we start a therapy
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  we would consider that a response
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  and then that's how we calculate the response rate
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  response rates can be then further classified into
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  stable disease
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  meaning that the tumors have stayed the same
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  a partial response
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  meaning that the tumors have gotten smaller
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  and then a complete response
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  meaning that the tumors have gone away completely
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  and then an aggregate of all those terms together
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  is something
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  that you may see as a clinical benefit rate
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  which means a CBR in a study just means that it
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  it encompasses one of those things as a
• 8:26
  as a whole group and then progressive disease uh
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  would mean unfortunately
• 8:31
  that the cancer has gotten larger
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  or is in new areas that it wasn't previously in
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  okay and then progression free survival
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  or PFS versus OS like
• 8:40
  I think that maybe is a little self explanatory
• 8:43
  but let's cover it just in case
• 8:44
  yeah so
• 8:45
  progression free survival is essentially
• 8:47
  how long you've been on the trial
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  before you have evidence that the
• 8:51
  the drugs not working anymore
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  whereas
• 8:53
  overall survival is how long the patient stayed alive
• 8:56
  no matter what happened after they came off the study
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  so for instance
• 8:59
  overall survival you know
• 9:01
  if you're on a trial for instance
• 9:02
  then you come off and you go on another trial
• 9:04
  we would still calculate the overall survival
• 9:06
  in the future
• 9:07
  and and account kind of for those
• 9:08
  those therapeutic modalities as well
• 9:11
  yeah especially if like
• 9:12
  the trial had like
• 9:13
  a specific end point where it was like OK
• 9:15
  this is you know
• 9:16
  you have 12 months on a study max
• 9:18
  and like that's it
• 9:19
  we take you off the drug at 12 months
• 9:20
  and then we follow I I know that was the case for like
• 9:22
  an adjuvant trial that I was in
• 9:23
  like years ago
• 9:24
  it was kind of like a okay
• 9:26
  like
• 9:26
  we're still gonna follow you no matter what happens
• 9:29
  as you know
• 9:29
  throughout the rest of your life
• 9:31
  so that makes sense right
• 9:32
  and why I guess
• 9:33
  why do you feel like as an oncologist
• 9:35
  why do you feel like
• 9:36
  it's important that you don't just look at
• 9:38
  for example the response rate
• 9:39
  because I know sometimes
• 9:40
  it can feel a little misleading to patients
• 9:42
  when they look at these studies
• 9:43
  to be like oh
• 9:44
  the response rate is only
• 9:45
  you know 40% or 30%
• 9:47
  like that doesn't look that great
• 9:48
  but then if you as a clinician are looking at
• 9:50
  you know
• 9:50
  overall survival or progression free survival durations
• 9:53
  like how do those kind of way into your decision
• 9:55
  and in saying oh
• 9:56
  this would actually be a pretty promising option
• 9:59
  a great question that comes up quite a bit and and
• 10:01
  and one of the things that I
• 10:02
  I would say is a challenge
• 10:03
  because when studies are are
• 10:06
  you know put out into the wide stream media or
• 10:09
  or biotech news
• 10:11
  they they will cling to these 1 1 metrics sometimes to
• 10:14
  to highlight uh
• 10:15
  a benefit of a study but
• 10:17
  you know
• 10:18
  response rate is really only taking into consideration
• 10:21
  one aspect
• 10:22
  of the overall picture of how a drug is working
• 10:25
  so uh
• 10:26
  for instance
• 10:27
  if you
• 10:27
  if you look at something like small cell lung cancer
• 10:29
  chemotherapy has a a very high response rate
• 10:32
  meaning that when you start chemotherapy the
• 10:35
  the tumors get much much smaller uh
• 10:37
  but there's a very quick relapse time
• 10:40
  so while the response rate is very good
• 10:42
  the progression free survival is not
• 10:44
  and that's important to keep in mind
• 10:46
  because in certain clinical situations
• 10:48
  you may need a really quick response rate
• 10:50
  if there's a chance that the
• 10:51
  the disease burden
• 10:52
  is going to cause clinical issues for the patient
• 10:55
  but when you think about progression free survival
• 10:58
  and more importantly overall survival
• 11:00
  are we actually making a difference
• 11:01
  in the amount of time we're giving a patient uh
• 11:04
  with these drugs so when
• 11:06
  when you think about these things
• 11:07
  you have to keep all of this in mind
• 11:08
  and the most important thing
• 11:10
  that I think we don't talk about enough
• 11:11
  is the side effects of the drugs
• 11:13
  so if you have something that has a
• 11:14
  a response rate that's high
• 11:16
  but a high chance of relapse
• 11:18
  or set a different way a
• 11:19
  a shorter progression free survival
• 11:21
  meaning a shorter time until you
• 11:22
  you relapse there's a high risk of toxicity
• 11:25
  all of these things
• 11:26
  need to be talked about with the patient
• 11:27
  because ultimately it's a decision between the
• 11:28
  the physician and the patient to see um
• 11:31
  that they understand those
• 11:32
  those data points and
• 11:32
  and what the risks and benefits are
• 11:34
  yeah like the cost versus the benefit
• 11:36
  all of that yeah
• 11:38
  okay um alright
• 11:39
  so rare cancer trials obviously
• 11:42
  we know uveal melanoma is rare
• 11:44
  um most of these studies
• 11:45
  have pretty small numbers of people
• 11:47
  enrolled in the trials you know
• 11:48
  as they're referencing their data
• 11:50
  right now
• 11:51
  why are rare cancer trials smaller
• 11:54
  so rare cancer trials are historically uh
• 11:57
  difficult because by virtue
• 11:59
  there are not as many patients with these cancers
• 12:01
  so if you take a cancer that's a little bit more common
• 12:06
  like non small cell lung cancer
• 12:08
  the numbers on the trials will be much larger
• 12:10
  because the patient populations are
• 12:11
  are much larger that are going to need a trial
• 12:14
  and have access to a trial
• 12:15
  uveal melanoma is very unique
• 12:17
  and that it's it's a rare cancer
• 12:18
  so when we think about trying to enroll the
• 12:21
  the patients onto the study
• 12:23
  it requires multiple sites
• 12:24
  across multiple geographic regions
• 12:26
  and takes a long time
• 12:27
  because there's just less patients to enroll
• 12:29
  we accept lower numbers on those studies
• 12:31
  and look at the data a little differently
• 12:33
  because we know that it's hard to enroll those studies
• 12:35
  the other thing that is now happening more and more
• 12:38
  is trying to characterize tumors in different ways
• 12:40
  so not as much in uveal melanoma
• 12:43
  but other
• 12:44
  other tumors that have common genetic mutations
• 12:48
  or things of that nature
• 12:50
  we enroll in something called basket studies
• 12:52
  where you enroll lots of different tumor types
• 12:54
  that have maybe a
• 12:55
  one similar characteristic
• 12:57
  and then
• 12:57
  see if you can benefit the whole patient population
• 13:00
  by using that common commonality to
• 13:03
  to treat them yeah no
• 13:05
  I think that's super cool um
• 13:07
  and I can see how like
• 13:08
  it could it could kind of be beneficial in each area
• 13:11
  like
• 13:12
  I mean I
• 13:12
  I know for example
• 13:14
  like
• 13:14
  Kimmtrak Hepzato
• 13:15
  like those got to approval
• 13:16
  and they're unique to uveal melanoma
• 13:19
  which is great um
• 13:20
  but it's also really good when we have um
• 13:23
  drugs that get approved and they happen to be approved
• 13:25
  for multiple different cancer types
• 13:26
  and also happen to work for uveal melanoma
• 13:28
  in some capacity um
• 13:30
  which I think that you know
• 13:31
  we're still kind of evolving in
• 13:32
  in the trials
• 13:32
  and seeing stuff that is actually effective
• 13:35
  in those ways um
• 13:37
  but I can see how that would also like
• 13:39
  yield kind of like
• 13:40
  look like a bigger study but
• 13:41
  when you kind of
• 13:42
  look at each little basket that you're putting it into
• 13:45
  the uveal melanoma basket
• 13:48
  is going to tend to be smaller
• 13:49
  just because our patient population is
• 13:51
  by nature smaller
• 13:53
  right which feels really weird
• 13:54
  because I feel like
• 13:55
  there's thousands of us that are metastatic
• 13:57
  like how small is that
• 13:58
  well
• 13:59
  and thankfully
• 14:00
  to credits like A Cure In Sight
• 14:02
  patient advocacy groups are so important
• 14:04
  I mean patient advocacy groups are important
• 14:06
  across all cancers or all diseases really
• 14:08
  but especially in these uh
• 14:10
  situations where
• 14:11
  you know if you weren't aware of this network
• 14:14
  you would you know
• 14:15
  have a hard time necessarily connecting with people
• 14:17
  because it is less common than other cancers
• 14:19
  yeah for sure
• 14:21
  okay so let's switch gears
• 14:22
  let's actually chat about these studies
• 14:24
  that came out during ESMO um
• 14:26
  we're gonna run through these
• 14:27
  uh we're gonna give kind of
• 14:28
  the most time to the ones that had
• 14:30
  maybe the most impact
• 14:31
  but I do wanna just give a heads up
• 14:33
  that if you have more questions
• 14:35
  like please
• 14:35
  don't hesitate to reach out to us at A Cure In Sight
• 14:38
  Contact@ACureInSight.org
• 14:39
  drop your comments and questions below
• 14:41
  we'll do our best to get those answers to you um
• 14:43
  by reaching out to Doctor Hadfield or other physicians
• 14:45
  and just keep in mind too
• 14:47
  that some of the things that we cover here um
• 14:50
  stay tuned for the rest of the year
• 14:52
  especially this first quarter
• 14:53
  in February
• 14:54
  we're going to be running a quarterly webinar
• 14:56
  our our Eye On The Expert webinar series
• 14:59
  and our first webinar
• 15:00
  is actually going to cover more in depth
• 15:02
  on this first study so
• 15:03
  Doctor Hadfield
• 15:04
  let's talk a little more about the Chopin trial
• 15:06
  and I'm like
• 15:07
  gonna kick myself I'm trying to only say Chopin
• 15:09
  not Chopin because I know it's Chopin um
• 15:13
  but yeah
• 15:14
  let's talk about that one
• 15:15
  um this one was Hepzato plus Ipi Nivo
• 15:18
  and this was done in Europe
• 15:19
  I believe this was done in the Netherlands
• 15:21
  so the the uh
• 15:23
  Chopin trial um
• 15:24
  combined uh
• 15:25
  percutaneous hepatic uh
• 15:26
  perfusion or Hepzato
• 15:28
  with ipilimumab plus nivolumab
• 15:30
  in metastatic uveal melanoma
• 15:32
  so this was a single center uh
• 15:34
  meaning it occurred at one place
• 15:35
  open label meaning that everyone knew what the drug was
• 15:38
  uh randomized study where uh
• 15:40
  the randomization um
• 15:42
  was essentially between patients
• 15:45
  to receive two courses of Hepzato
• 15:47
  which is this perfusion uh
• 15:49
  in weeks 1 and 7
• 15:50
  with or without alternating treatments
• 15:51
  of ipilimumab and nivolumab
• 15:53
  which if you're not familiar
• 15:54
  are immune checkpoint inhibitors
• 15:56
  which have been used in uveal melanoma
• 15:57
  but uh uh
• 15:58
  also more so in cutaneous melanoma in the past
• 16:02
  and what this essentially showed
• 16:03
  that progression free survival at one year
• 16:06
  in the combination group was 54.7%
• 16:09
  versus 15.8% in the control group
• 16:12
  so this is very important data to
• 16:14
  to go over basically what we
• 16:16
  what we showed here
• 16:17
  was pretty significant and interesting
• 16:20
  difference between progression free survival
• 16:22
  and those receiving immunotherapy
• 16:23
  plus the hepatic perfusion
• 16:25
  as opposed to just the hepatic perfusion alone
• 16:28
  uh overall survival at one year was
• 16:29
  was almost the same 82.8% in the uh
• 16:32
  combination group versus
• 16:34
  82.2%
• 16:36
  in the control arm and control arm here uh
• 16:39
  just a
• 16:40
  if you hear that reference
• 16:41
  is the
• 16:41
  without the Ipi Nivo
• 16:45
  okay so control arm
• 16:46
  meaning they only had the two rounds of the Hepzato
• 16:49
  Yep that's right
• 16:50
  the the PHP
• 16:51
  the percutaneous hepatic perfusion
• 16:53
  oh my goodness
• 16:54
  I can say it um
• 16:56
  okay and then what about our response rate
• 16:58
  do we have a response rate for this study
• 17:00
  so the
• 17:00
  the best overall response rate in the combination group
• 17:03
  was was pretty impressively
• 17:04
  76.3 versus 39.5 in the in the control arm
• 17:09
  so just for reference like
• 17:11
  is Hepzato I mean
• 17:12
  Hepzato got approved and
• 17:14
  and it's also been approved as chemosat in Europe
• 17:17
  um it got approved on this original
• 17:19
  you know on this original response rate like
• 17:21
  you know and
• 17:22
  and actually we should
• 17:23
  we should kind of give the caveat
• 17:24
  that the Hepzato treatment
• 17:26
  the chemosat treatment
• 17:27
  they were approved contingent on the trial data
• 17:30
  of six consecutive treatments
• 17:32
  this is only showing two Hepzato treatments
• 17:34
  so like
• 17:35
  I feel like we have to take some of that like
• 17:36
  grain of you know
• 17:37
  some of that response rate with a grain of salt
• 17:39
  knowing that they only did like
• 17:40
  a small chunk of the
• 17:42
  how could we alternate these treatments
• 17:44
  yeah and I
• 17:45
  I think um
• 17:47
  there yes
• 17:48
  that that is a very
• 17:49
  very good point and
• 17:50
  and it raises another point that
• 17:51
  when you're reviewing studies in general
• 17:53
  it's very hard and and
• 17:55
  and in many ways
• 17:56
  not fair to compare different trials to each other
• 17:59
  because each trial had was designed statistically to
• 18:04
  to answer one question and it does not
• 18:07
  you know cross over to other trials
• 18:09
  each one has their own answer
• 18:10
  the same questions for sure
• 18:11
  exactly and it statistically
• 18:12
  they don't answer the same question
• 18:13
  the patient populations may be different
• 18:15
  the enrollment may different
• 18:16
  exclusion and inclusion criteria
• 18:17
  so lots of things to consider
• 18:19
  but at least based on this study
• 18:20
  we see a a
• 18:21
  a remarkably uh
• 18:23
  in improved progression free survival
• 18:24
  and overall response rate with the combination
• 18:27
  yeah and okay
• 18:28
  so like
• 18:29
  there's a lot of qualms in uveal melanoma
• 18:32
  about people who are like very
• 18:35
  just hardcore anti Ipi Nivo
• 18:37
  they're very like
• 18:38
  very afraid of it because of the side effects
• 18:39
  they hear a lot of the
• 18:40
  the really big hard side effect stories
• 18:42
  which I know do exist right
• 18:44
  Ipi Nivo does tend to be a little bit of a harsher
• 18:46
  option in immunotherapies
• 18:48
  even for cutaneous patients
• 18:50
  but maybe we kind of caveat that with the okay
• 18:53
  but now we know about fiber
• 18:55
  so maybe that helps that's
• 18:57
  that's an option um
• 18:59
  but also like
• 19:00
  what about the study was unique about what they
• 19:02
  like how they dosed Ipi Nivo
• 19:03
  did they do a normal dose
• 19:05
  did they do kind of a lower dose
• 19:07
  Castle Biosciences is a proud sponsor of this
• 19:09
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• 19:11
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• 19:13
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• 19:15
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• 19:17
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• 19:19
  individualize the management of your disease
• 19:22
  to learn more visit Castlebiosciences.com
• 19:25
  it's challenging when you think about
• 19:28
  uh uveal melanoma because um
• 19:30
  when when we talk about uh
• 19:31
  Ipi Nivo dosing
• 19:33
  a very important caveat is that nivolumab
• 19:35
  does not have a dose dependent toxicity uh
• 19:38
  nor do any of the other PD-1 inhibitors
• 19:40
  so uh
• 19:41
  and and that would include things like pembrolizumab
• 19:43
  durvalumab
• 19:44
  but the ipilimumab does so
• 19:47
  you know and
• 19:48
  and you patients may hear
• 19:49
  you know full dose Ipi Nivo
• 19:51
  which is uh
• 19:52
  3 milligrams per uh
• 19:53
  kilogram and then 1 mg of the PD-1 inhibitor
• 19:56
  and then flip dose IPI would be the opposite of that
• 19:59
  so
• 20:00
  you know it it
• 20:01
  this study long story short
• 20:04
  did not show any emerging new safety
• 20:07
  side effects or toxicities with the combination
• 20:10
  or with the the two modalities on their own
• 20:13
  um but I do think it
• 20:14
  it raises a really important point that um
• 20:16
  immunotherapy toxicities is something that we can't uh
• 20:19
  we can't overlook and in many ways
• 20:22
  is a challenge for the patient and the
• 20:24
  the um
• 20:26
  oncoligist
• 20:26
  because we don't have a great way of predicting them
• 20:28
  so we don't know um
• 20:31
  we know when you give Ipi Nivo
• 20:33
  there's a 50% chance that you have a grade 3 toxicity
• 20:35
  meaning that we have to stop the drug
• 20:38
  stop the drugs start steroids
• 20:40
  high dose steroids and and
• 20:41
  and try and uh
• 20:42
  reduce whatever inflammatory response is
• 20:44
  is going on
• 20:45
  and there's like
• 20:45
  a 90% chance of having any toxicity at all
• 20:48
  so you know the
• 20:50
  these are these are understandably scary numbers
• 20:53
  but at least this study was in line
• 20:55
  that this is a safe regimen to to give
• 20:59
  yeah absolutely
• 21:00
  um okay
• 21:01
  so like for patients who hear these numbers
• 21:03
  about the Chopin trial um
• 21:05
  obviously this trial has not occurred in the States
• 21:07
  and my understanding is that it's not like
• 21:09
  going to enroll in the States
• 21:10
  this is more informative like
• 21:12
  for oncologists to hear and know about uh
• 21:14
  so what could this mean for like
• 21:16
  kind of the day to day decision making
• 21:17
  when you're treating a uveal melanoma patient
• 21:20
  and kind of how they decide what therapy to pursue
• 21:23
  well I think um
• 21:25
  this this is a a
• 21:26
  a really good study
• 21:27
  to mention to your uveal melanoma oncologist
• 21:30
  and say that you you saw the data
• 21:31
  and you saw that there was an improved response uh
• 21:34
  with uh
• 21:35
  adding immunotherapy to to Hepzato
• 21:38
  and have a conversation
• 21:41
  every single patient is different
• 21:42
  there's gonna be risks and benefits
• 21:43
  you know for instance
• 21:44
  we were talking before we
• 21:45
  we started this conversation about um
• 21:47
  you know past toxicities
• 21:49
  may dictate whether or not you're a good candidate
• 21:50
  or not to restart immunotherapy
• 21:52
  which is is not a trivial thing to talk through
• 21:54
  but it's definitely a
• 21:55
  an area where you should have a
• 21:56
  a conversation with your oncologist and and
• 21:58
  and see what may or may not be right for you
• 22:00
  in terms of standard of care options
• 22:01
  here in the United States
• 22:03
  yeah okay
• 22:04
  well just briefly
• 22:05
  like what's your opinion on why
• 22:07
  combining the immunotherapy with Hepzato
• 22:09
  and you know
• 22:10
  like cause Hepzato
• 22:12
  I guess I'll just I'll just summarize
• 22:14
  and you can correct me or
• 22:15
  or you can summarize but like
• 22:16
  you know Hepzato is chemo based
• 22:19
  and it's specifically localized chemo to the liver
• 22:22
  we've talked about it a lot here on the podcast
• 22:24
  we've had lots of webinars and lots of speakers discuss
• 22:26
  what is Hepzato how does it work
• 22:28
  so why do you think just kind of opinion wise
• 22:30
  why do you think doing the Hepzato
• 22:32
  with the immunotherapy
• 22:33
  has the promising potential that it shows
• 22:36
  there's certainly lots of theories behind this
• 22:38
  and we we kind of
• 22:39
  get into the big themes of immuno-oncology in 2025
• 22:44
  and going into 2026 in the last few years
• 22:46
  we have cold tumors
• 22:47
  which are essentially tumors where the immune system
• 22:51
  for multitude of reasons is not getting into the tumor
• 22:54
  um and then we have hot tumors which uh
• 22:57
  if we think of like
• 22:57
  cutaneous melanoma is very immunogenic or
• 23:00
  or a hot tumor
• 23:01
  meaning that when you prime the immune system
• 23:03
  with immune checkpoint inhibitor therapies
• 23:04
  it's able to do what it's supposed to do right away
• 23:07
  I think when you think about something like Hepzato
• 23:09
  we've seen other combinations of chemotherapy with
• 23:12
  with immunotherapy we've seen other uh
• 23:14
  drugs such as VEGF inhibitors which uh
• 23:16
  interfere with the uh
• 23:17
  vascular angiogenesis or blood vessel growth in tumors
• 23:21
  and I think ultimately
• 23:22
  I don't think we have a
• 23:24
  an exact understanding of the mechanism
• 23:25
  but it's probably uh
• 23:27
  that we're the
• 23:28
  the killing of the cancer cells is
• 23:30
  is allowing a local inflammatory response
• 23:32
  that then
• 23:32
  can be propagated further by the checkpoint inhibitors
• 23:34
  so it's it's really a synergistic
• 23:36
  but I think there is a lot to
• 23:38
  to the understanding of that mechanism
• 23:39
  that we have yet to figure out
• 23:41
  yeah for sure
• 23:41
  I guess like
• 23:42
  the way that I'm understanding what you said
• 23:43
  is just basically
• 23:44
  like the cold tumors of uveal melanoma
• 23:48
  when they're killed for lack of a better term
• 23:52
  by the Hepzato it kind of um
• 23:54
  like they kill the cells right
• 23:56
  and then the the cells
• 23:57
  our body has to dispose of those dead cells
• 23:59
  that's part of like
• 24:00
  how the cells work I'm like
• 24:02
  trying to think back to seventh grade biology
• 24:04
  but when it picks up
• 24:06
  those dead cells that are cancer cells
• 24:08
  they're now like
• 24:09
  no longer invisible they're not cloaked anymore
• 24:11
  and so the immune system has a better chance
• 24:14
  I guess of like
• 24:15
  seeing them so to speak
• 24:17
  yeah
• 24:17
  tumor I think
• 24:18
  we like to think of as a ball of cells
• 24:20
  that is just growing but it's really not true
• 24:22
  it really what it is
• 24:23
  is it's a ball of cells
• 24:24
  that's growing around dead cancer cells
• 24:26
  fibrotic tissue like scar tissue
• 24:28
  it gets very like
• 24:29
  walled off and matted we
• 24:31
  we talk about this as the tumor microenvironment
• 24:33
  and when you think of that
• 24:35
  you're exactly right when you start
• 24:37
  you know at least theoretically
• 24:38
  when you start using something
• 24:39
  that will break into that environment
• 24:41
  and release some of these
• 24:42
  we call them neoantigens or the proteins
• 24:44
  that the immune system will actually see and attack
• 24:47
  um we get a better response and
• 24:48
  and I I think we see that here with the
• 24:50
  with the Chopin trial
• 24:52
  yeah absolutely
• 24:53
  okay well
• 24:54
  I wanna move on to our next study
• 24:56
  but like I said you guys like
• 24:57
  if you're listening and you're like
• 24:58
  wait wait wait
• 24:58
  no like
• 24:59
  tell me more like
• 25:00
  I wanna hear more about this
• 25:01
  please tune in to our first quarter webinar
• 25:03
  we are gonna be covering the Chopin trial
• 25:05
  in more depth
• 25:05
  because this is such a clinically relevant
• 25:07
  set of information that we
• 25:09
  as patients need to be aware of
• 25:10
  and that we I mean
• 25:12
  I just I have
• 25:13
  I have a lot of hope personally
• 25:14
  that we're going to see more patients able to
• 25:16
  kind of enact this similar protocol
• 25:18
  over the course of their treatment
• 25:20
  and that we'll
• 25:21
  we'll see some really good results from it
• 25:23
  but let's move on to the um
• 25:25
  IMA203 t cell or the Immatics therapy trial
• 25:29
  um this is a pretty complex therapy
• 25:31
  and we're I mean
• 25:33
  I guess I kind of thought of it as like
• 25:35
  this is maybe similar to TIL therapy
• 25:38
  is that I mean
• 25:38
  is that similar or or not really
• 25:41
  no um
• 25:42
  no similar concept so uh
• 25:44
  the this
• 25:45
  this study uh
• 25:46
  was the Presidential Symposium abstract presented by uh
• 25:50
  Sapna Patel uh
• 25:51
  from the university of Colorado um
• 25:53
  who's been really instrumental in in
• 25:54
  in bringing this therapy forward
• 25:57
  uh so
• 25:57
  the IMA203
• 25:59
  is a prame directed t cell receptor therapy
• 26:02
  in patients who had previously treated advanced
• 26:06
  metastatic uveal melanoma so what this therapy is um
• 26:09
  when we think about tumor infiltrating lymphocytes um
• 26:12
  what we're doing in that situation is
• 26:14
  we are lymphocytes
• 26:15
  being the immune cells that kill cancer cells
• 26:18
  we are taking tumor out and we're
• 26:21
  we're taking the immune cells out of that
• 26:23
  and then we're increasing them
• 26:25
  and then outside the body
• 26:27
  and then putting them back in to treat the patient um
• 26:30
  what t cell uh
• 26:33
  we we would call these BiTE therapies
• 26:35
  or bispecific t cell engaging therapies
• 26:38
  what what we are doing with
• 26:39
  with these therapies and there's
• 26:41
  there's a multitude of uh
• 26:42
  them that are in clinical development
• 26:44
  across multiple solid tumors
• 26:45
  as well as uh
• 26:47
  multiple standard of care um
• 26:48
  targeted therapies what
• 26:50
  what it's doing is the there's a protein
• 26:52
  that's being expressed on the tumor cells
• 26:55
  this is the prame derived peptide protein
• 26:58
  and then on the other side of the protein
• 27:00
  is something that binds the t cells
• 27:02
  the t cells that are circulating in your body
• 27:04
  so getting back to that concept of cold
• 27:08
  tumor micro environments you know
• 27:09
  I mean when you give a checkpoint inhibitor
• 27:11
  and the immune cells are not getting into the tumor
• 27:13
  this is a way to hone the t cells to the
• 27:17
  the tumor uh
• 27:19
  and try and propagate that immune response that way
• 27:21
  very very promising therapy
• 27:23
  this is a very important study
• 27:25
  very very interesting results
• 27:27
  so that is essentially the gist of
• 27:29
  of the the mechanism of action
• 27:32
  before we get into the study results
• 27:34
  how were the patients like
• 27:36
  who entered the study
• 27:37
  kind of generally doing from like a
• 27:38
  I don't know like
• 27:39
  current disease status or like physical
• 27:41
  I don't know physical fitness physical health
• 27:44
  so um
• 27:45
  the study enrolled 74
• 27:47
  we would call them heavily pre treated patients
• 27:49
  which means that they had a median uh
• 27:51
  or or average three prior lines of therapy
• 27:53
  so these are patients who have really exhausted most
• 27:57
  if not all standard of care options uh
• 27:59
  for for uveal melanoma
• 28:00
  and the um
• 28:02
  yeah so
• 28:03
  so that
• 28:04
  it was a pretty heavily pre treated patient population
• 28:07
  uh huh
• 28:08
  okay so let's talk about these numbers
• 28:10
  what was our response
• 28:11
  yeah I guess just
• 28:12
  just to to um
• 28:15
  summarize again the study uh
• 28:17
  was patients with recurrent or refractory
• 28:19
  uveal melanoma um
• 28:21
  in solid tumors where they were uh
• 28:23
  HLA-A0201 positive and prame positive uh
• 28:27
  and included uh
• 28:28
  uveal melanomas with prior Tebentafusp responses
• 28:32
  so the study enrolled as I mentioned
• 28:34
  74 uh
• 28:35
  heavily pretreated patients
• 28:36
  and the most common treatment related adverse event was
• 28:39
  cytopenias that occurred in almost all patients
• 28:42
  that were enrolled on the study
• 28:43
  cytopenia meaning
• 28:44
  that you have a decrease in your white blood cells
• 28:46
  your red blood cells or your platelets
• 28:47
  and then cytokine release
• 28:49
  syndrome was another important toxicity
• 28:51
  so what this essentially showed was
• 28:54
  this is very common
• 28:55
  across all t cell engaging therapies
• 28:57
  like this
• 28:58
  when you give these therapies
• 28:59
  you create an immune response uh
• 29:01
  that's a little different than what you would think of
• 29:02
  with an immune checkpoint inhibitor
• 29:04
  um
• 29:04
  you're essentially creating a lot of cytokines in this
• 29:07
  in a short amount of time
• 29:08
  and this can lead to low blood pressure
• 29:09
  can lead to fevers it can lead to um
• 29:11
  it can be uh quite uh
• 29:14
  serious uh from a clinical standpoint
• 29:16
  so we monitor patients very
• 29:17
  very closely for that
• 29:18
  so CRS occurred in 95% of patients on the study
• 29:21
  it was mostly low grade um
• 29:23
  meaning that it wasn't uh
• 29:24
  to the point where uh people were clinically unstable
• 29:28
  um and then of
• 29:29
  of the most important findings
• 29:31
  for the uveal melanoma community
• 29:32
  is that a confirmed
• 29:33
  objective rate of response was achieved in 67% of the
• 29:36
  uh uveal melanoma efficacy evaluable patients
• 29:38
  which was uh 10 out of 15 with one uh
• 29:41
  patient having an ongoing unconfirmed partial response
• 29:44
  and then all patients
• 29:45
  16 out of 16 experienced tumor shrinking
• 29:48
  which is pretty remarkable if
• 29:50
  if you if you think of that
• 29:51
  that to me and I think to the larger community
• 29:53
  shows that there's definitely a signal there
• 29:55
  that this is doing something
• 29:56
  although very very small numbers
• 29:58
  in a phase 1 studies we talked about before
• 30:00
  and then the median progression free survival was
• 30:02
  eight and a half months
• 30:03
  with a median overall survival of 16.2 months
• 30:06
  so very very uh
• 30:08
  important study that is now uh
• 30:09
  going into the phase 2 portion of the study um
• 30:12
  and that's gonna be enrolling I
• 30:13
  I believe it's already enrolling patients
• 30:15
  yeah that's fantastic
• 30:17
  um I actually have the
• 30:18
  the luck of knowing someone who
• 30:20
  I'm pretty sure is included in this data
• 30:21
  and she has
• 30:23
  one of the best response rates
• 30:24
  that they have in the study
• 30:25
  and so it's been really cool like to
• 30:27
  to know that that is um
• 30:29
  going well for her and I'm
• 30:30
  I'm thrilled that they're able to continue enrolling
• 30:32
  because I think for a little while last year
• 30:34
  it seemed like there was kind of a
• 30:36
  a lull in in if they were going to continue on with
• 30:40
  with uveal and so I'm glad they are
• 30:42
  that's really really um
• 30:43
  promising to hear
• 30:44
  yeah yeah
• 30:45
  very very
• 30:45
  very exciting data I mean uh
• 30:47
  I think uh
• 30:49
  and Doctor Patel presented this uh
• 30:51
  at ESMO
• 30:52
  you know seeing
• 30:53
  response of tumor shrinkage in that many patients is
• 30:55
  is uh
• 30:56
  pretty remarkable and
• 30:58
  and and certainly very uh
• 30:59
  enthusiastic for for what may be shown in the
• 31:02
  the larger trial
• 31:03
  yeah absolutely
• 31:05
  okay so you mentioned the CRS um
• 31:07
  common responses like
• 31:08
  just the common side effects
• 31:10
  and you also mentioned
• 31:11
  I don't actually know if we mentioned this like
• 31:13
  just for the like
• 31:13
  how this is done um
• 31:16
  it starts with kind of figuring out and um
• 31:19
  making the cells but then there's some elements of like
• 31:22
  chemo and hospitalization that are needed for like
• 31:24
  doing this treatment is that correct
• 31:26
  yeah so uh
• 31:28
  basically you
• 31:29
  you undergo very similar to TIL
• 31:31
  as you've mentioned before
• 31:33
  just slightly different uh
• 31:34
  you you undergo cytoreduction
• 31:37
  which is uh
• 31:38
  or lymphodepletion rather
• 31:40
  which is basically like
• 31:41
  you're getting rid of some of the lymphocytes
• 31:42
  that are there already in your body to
• 31:43
  to make room for this this infusion of uh
• 31:46
  lymphocytes then you are hospitalized to
• 31:47
  to monitor you for that
• 31:49
  cytokine release syndrome that can potentially occur
• 31:51
  so it's a little bit different than other therapies
• 31:53
  and I think
• 31:53
  something that we have to definitely keep an eye on
• 31:55
  because when you you think about these therapies uh
• 31:59
  they're very very promising
• 32:00
  and they're very very
• 32:01
  you know offer a lot of hope for the future
• 32:03
  but
• 32:03
  we have to think about how to give these therapies to
• 32:05
  to more and more patients around the country
• 32:07
  in the world because
• 32:08
  I do worry that some of these therapies will be
• 32:10
  isolated to larger centers
• 32:11
  for a long period of time
• 32:13
  I mean this is still a clinical trial
• 32:14
  but you know
• 32:15
  assuming or hoping that this goes on to become approved
• 32:18
  that that is definitely a concern
• 32:20
  yeah absolutely
• 32:21
  um and I think too
• 32:22
  like this is one of those treatments too
• 32:25
  that maybe patients would be like
• 32:27
  listening and and kind of weighing okay
• 32:29
  I'm HLA positive I'm prame positive
• 32:31
  like maybe this would be an option for me
• 32:33
  this sounds pretty intense
• 32:35
  um how
• 32:36
  like as an oncologist
• 32:37
  do you feel
• 32:37
  like you can help weigh the intensity versus
• 32:40
  like the possible benefit
• 32:42
  like is this something that is an ongoing treatment
• 32:44
  or is it kind of more of a one time thing
• 32:45
  I mean it's a one time thing
• 32:46
  but it's it's
• 32:47
  it's very um
• 32:49
  it it is very intensive
• 32:50
  so I mean it
• 32:50
  it falls into the realm of cellular therapies where we
• 32:53
  we do have a high risk CRS
• 32:55
  we have a high risk uh
• 32:57
  just by giving someone the
• 32:59
  the lymphodepleting chemotherapy
• 33:00
  there's potential complications for that
• 33:02
  so I mean
• 33:03
  it really is something where you have to
• 33:06
  you know talk to your oncologist and and
• 33:07
  and make sure that you're a good candidate
• 33:10
  you know any of the centers that are doing things like
• 33:11
  tumor infiltrating lymphocytes
• 33:13
  or these trials are are
• 33:14
  obviously
• 33:15
  the experts in determining who would
• 33:16
  and wouldn't be a good fit
• 33:17
  but um
• 33:18
  it is not a trivial trial to enroll in
• 33:20
  and these aren't therapies that are
• 33:21
  you know
• 33:22
  necessarily a good fit for everybody
• 33:24
  yeah for sure
• 33:25
  um okay
• 33:26
  well let's move on to the next study
• 33:28
  this one was really cool and
• 33:29
  I feel like we could definitely talk about it for ages
• 33:31
  so I I'm gonna have to come back to that one
• 33:33
  like with another like
• 33:34
  another physician or like in a webinar maybe
• 33:36
  like I just feel like it's really neat
• 33:38
  yeah but let's talk
• 33:40
  let's talk about the plume trial
• 33:41
  which was the pembro
• 33:42
  is it pembrolizumab and lenvatinib
• 33:47
  and like kind of
• 33:48
  I guess the goal of this one is really
• 33:49
  let's cover some realistic post event of us for
• 33:52
  Kimmtrak options
• 33:53
  right so yeah
• 33:55
  when when we think about uveal melanoma
• 33:57
  you know once we get into the category of patients
• 34:00
  that are not as similar to cutaneous oncology
• 34:02
  with BRAF when we have to divide into HLA positive
• 34:04
  and HLA negative patients
• 34:05
  and those that unfortunately
• 34:07
  don't have HLA-A0201 positivity
• 34:10
  we we need to well
• 34:12
  for all patients but
• 34:13
  you know those that can't get Tebentafusp
• 34:15
  we're actively trying to think about other new
• 34:18
  potential therapies so uh
• 34:19
  this the plume study
• 34:21
  a single arm phase 2 trial of pembro
• 34:23
  which is a an immune checkpoint inhibitor
• 34:25
  and lenvatinib
• 34:27
  which is a VEGF inhibitor that I had mentioned before
• 34:30
  so what lenvatinib
• 34:33
  basically so the
• 34:35
  the rational behind the
• 34:36
  the trial is similar to what we were talking about with
• 34:40
  uh
• 34:40
  the Chopin trial
• 34:42
  yes
• 34:43
  so this is a multi-kinase inhibitor
• 34:44
  acts on multiple different kinases in the
• 34:45
  in the cell and
• 34:46
  and what you're doing is that
• 34:48
  you're hoping that
• 34:49
  you're changing the tumor microenvironment
• 34:51
  in a way
• 34:51
  that will restructure some of these blood vessels and
• 34:54
  and allow uh immune cells in
• 34:56
  so that's this is something that um
• 34:59
  you know we've the
• 35:01
  these synergistic combinations have been uh
• 35:04
  you know thought of and explored for a while now
• 35:06
  so the the patient was uh
• 35:09
  or the the study was two cohorts uh
• 35:11
  assessed HLA-A0201 negative patients
• 35:14
  and Tebentafusp naive
• 35:15
  it obviously makes sense to group those together
• 35:18
  and then HLA-A0201
• 35:19
  positive patients pretreated with Tebentafusp
• 35:22
  and then patients received pembrolizumab
• 35:24
  for a maximum of 35 cycles um
• 35:28
  standard dosing every 3 weeks
• 35:29
  plus lenvatinib which is 20 mg a day
• 35:32
  and then um
• 35:35
  they had imaging every uh
• 35:37
  every nine weeks until progression
• 35:38
  so what the what the study showed
• 35:40
  was
• 35:40
  that all patients were followed for more than 27 weeks
• 35:43
  um and 15 progressions were observed in Cohort 1
• 35:46
  which was that combination uh
• 35:48
  corresponding to a 27
• 35:49
  progression free survival of 31.8% uh
• 35:52
  cohort 2 uh had 11 progressions in that 27 week period
• 35:57
  uh with a progression free survival of 60.7% um
• 36:00
  so the you know
• 36:04
  difference is there in in
• 36:05
  in progression free survival for sure
• 36:07
  but um a very small study with very small numbers
• 36:10
  yeah you know
• 36:11
  but also like decent numbers
• 36:14
  yeah yeah
• 36:15
  I guess I think that's pretty decent
• 36:16
  like especially for the cohort 2
• 36:18
  the pre treated Tebentafusp
• 36:19
  but even for the people who are HLA
• 36:21
  cause I know that's that's a common
• 36:23
  it's just a hot topic in our
• 36:24
  our community
• 36:25
  especially since we've gotten Kimmtrak approved
• 36:27
  is okay sure
• 36:28
  Kimmtrak that could be great for somebody
• 36:30
  the HLA positive especially for
• 36:31
  you know the patients whose trial
• 36:33
  who can enroll in a trial
• 36:34
  that is HLA positive and or prame dependent
• 36:37
  but it kind of feels a little like
• 36:39
  but what about me right
• 36:40
  me right
• 36:41
  HLA O2 negative
• 36:42
  like what's out there for me
• 36:43
  this is at least something
• 36:45
  it's maybe not the highest numbers
• 36:46
  but it is something and it's
• 36:48
  I feel like that's that's a pretty significant number
• 36:50
  the 30
• 36:51
  it is 30 ish
• 36:51
  31%
• 36:52
  it is
• 36:53
  but um
• 36:54
  the things to keep in mind
• 36:56
  is that this was a comparative study
• 36:57
  it wasn't it wasn't a randomized study
• 36:59
  so we're not comparing these two groups necessarily
• 37:01
  it's just a comparison
• 37:02
  which can kind of be
• 37:03
  it's their cohorts as opposed to arms
• 37:06
  and I think it hints the the
• 37:07
  the fact that we don't have great therapies for
• 37:09
  for patients in this in this uh
• 37:11
  category so uh
• 37:13
  we we are looking for novel combinations
• 37:15
  and I I think that this
• 37:16
  this trial fits that so yeah um
• 37:19
  definitely something to to keep in mind
• 37:21
  what about like
• 37:22
  the safety reality of um
• 37:23
  this combination of like
• 37:25
  the checkpoint inhibitor and the VEGF
• 37:27
  the VEGF drug
• 37:28
  so uh
• 37:28
  the safety and uh uh
• 37:30
  the safety was consistent with this kind
• 37:33
  this is a combination
• 37:34
  that's been used in other solid tumors already
• 37:36
  so um not
• 37:38
  not a complete novel combination on in of itself
• 37:40
  there was no new or or different uh toxicities
• 37:43
  lenvatinib is is uh
• 37:45
  admittedly a pretty tough drug to take uh
• 37:47
  so uh there's
• 37:49
  there's uh quite a few potential side effects that are
• 37:52
  warrant dose reductions and
• 37:54
  and stopping uh
• 37:54
  so
• 37:55
  76% of patients on this trial
• 37:57
  had to have dose reductions in lenvatinib
• 37:58
  which is is pretty consistent with
• 38:00
  with other trials um
• 38:01
  and then pembrolizumab obviously you have the um
• 38:05
  the potential for
• 38:06
  immune checkpoint inhibitor toxicities
• 38:07
  but nothing that was new
• 38:08
  or different than what's been demonstrated in the past
• 38:11
  okay alright
• 38:12
  so then for for this one
• 38:14
  what do you feel like
• 38:15
  is the biggest takeaway from this specific study
• 38:17
  for us like kind of moving forward
• 38:19
  I think the the
• 38:20
  the biggest takeaway for this study is um
• 38:23
  you know something that warrants further exploration
• 38:28
  as a combination but also something where if you
• 38:30
  if you unfortunately find yourself without options
• 38:33
  something you should talk to your oncologist about
• 38:35
  and see I mean
• 38:35
  these are FDA approved drugs
• 38:37
  that could technically be the rationale if
• 38:40
  if there aren't another
• 38:42
  no other standard of care treatment options available
• 38:44
  you can you can consider this combination off
• 38:46
  off off label
• 38:47
  it's not FDA approved and hasn't
• 38:48
  hasn't undergone a randomized trial
• 38:50
  but um something to
• 38:51
  talk about the risks and benefits of doing that
• 38:52
  with your oncologist
• 38:54
  yeah absolutely
• 39:26
  alright well um
• 39:27
  this next one
• 39:28
  I just wanna like really briefly touch on this
• 39:30
  cause I know
• 39:30
  this does focus a little more on protecting vision
• 39:33
  but this one is the dur dur
• 39:35
  oh my goodness Darovasertib
• 39:37
  I can say it the Darovasertib trial
• 39:39
  and this one was I think
• 39:41
  isn't it one of the arms of the Ideaya trial
• 39:43
  is that the correct term so
• 39:46
  this one is specifically talking about
• 39:49
  treating the primary disease
• 39:50
  meaning the eye itself
• 39:51
  but what do you feel like
• 39:52
  the benefits are of something like this
• 39:54
  being an adjunct therapy that we're seeing numbers in
• 39:57
  just to give the background
• 39:59
  um this was a phase 2 study of uh
• 40:01
  Darovasertib as neoadjuvant therapy
• 40:03
  meaning before surgery in primary uh
• 40:05
  uveal melanoma patients
• 40:06
  requiring either enucleation or uh
• 40:09
  plaque brachytherapy um
• 40:10
  and the primary endpoint was uh
• 40:12
  enucleation prevention meaning that you've
• 40:14
  you've shrunk the tumor down
• 40:16
  and you no longer have to go with such a drastic
• 40:19
  uh surgical intervention
• 40:20
  so in this uh
• 40:22
  in the population of patients
• 40:23
  90 primary uveal melanoma patients
• 40:26
  received uh
• 40:26
  Darovasertib at 300 mg twice daily in 28 days cycles
• 40:30
  the efficacy in the population was
• 40:33
  59% of patients became eligible for enucleation
• 40:35
  prevention
• 40:37
  for patients with available paired simulations and
• 40:40
  the reduction of the tumor essentially
• 40:43
  so so
• 40:44
  so really what what
• 40:45
  what they showed in
• 40:46
  in this study was that you can have a
• 40:49
  a cohort of patients that can avoid enucleation by um
• 40:52
  giving this therapy so I think
• 40:54
  you know admittedly a
• 40:56
  an area that is a practicing oncologist I see less of
• 40:58
  because I I don't
• 40:59
  I don't see as many of the
• 41:01
  the neoadjuvant patients
• 41:02
  but it's certainly something that
• 41:03
  your ocular oncologist um
• 41:04
  and medical oncologist should both be aware of
• 41:07
  this data because it's a
• 41:08
  it's important
• 41:09
  this is something where you could potentially uh
• 41:11
  reduce the risk of
• 41:12
  or reduce the need of a very uh
• 41:15
  intense intervention to treat your your primary disease
• 41:18
  yeah absolutely
• 41:19
  I mean this is the kind of trial that like
• 41:20
  if I go back five and a half years to
• 41:22
  when I was diagnosed with a massive
• 41:23
  barely plaque eligible tumor in my eye
• 41:26
  and knowing like
• 41:27
  what radiation damage I experienced because of the
• 41:29
  just the sheer size of the tumor
• 41:32
  I could see this have you know
• 41:33
  having been something that could have potentially
• 41:35
  avoided eventual enucleation
• 41:37
  for me
• 41:37
  because if we can shrink the tumor
• 41:39
  and reduce how much radiation is used to treat it
• 41:42
  then I mean
• 41:43
  that would be good
• 41:43
  I know there's been a little bit of noise
• 41:45
  around this specific trial
• 41:47
  and kind of I don't
• 41:48
  I don't know if they still have this arm
• 41:49
  I think they did temporarily
• 41:51
  but like
• 41:51
  kind of
• 41:51
  going from the neo adjuvant to the adjuvant setting
• 41:54
  where they I think
• 41:55
  were allowing patients to and
• 41:57
  and don't quote me on this guys
• 41:58
  but like
• 41:59
  have you heard of that like
• 41:59
  where they were like uh
• 42:00
  patients who who did well
• 42:02
  neo adventantly
• 42:03
  they let them keep taking it temporarily
• 42:05
  yeah taking the Daro drug
• 42:07
  yeah yeah
• 42:09
  the the crossover to the other arm
• 42:10
  basically where you you get adjuvant therapy yes
• 42:13
  I don't know if anything has been published on that yet
• 42:16
  OK yeah
• 42:17
  I'm not sure still more to come
• 42:18
  more to come for sure
• 42:19
  what do you think is the potential for something like
• 42:22
  you know
• 42:22
  to eventually maybe tap into that adjuvant setting
• 42:25
  like from an oncology standpoint
• 42:27
  well I mean I I
• 42:28
  I think any
• 42:29
  anytime you're exploring a neoadjuvant therapy
• 42:31
  that has the potential to reduce
• 42:33
  the definitive therapy
• 42:35
  but also may have some role in adjuvant intent
• 42:39
  therapy to prevent disease recurrence or
• 42:41
  you know prevent
• 42:42
  uh
• 42:43
  distant
• 42:44
  uh metastasis free survival or
• 42:46
  or improved distant metastasis free survival
• 42:49
  I think that's uh
• 42:50
  that's you know
• 42:51
  very very important and and
• 42:53
  and you know
• 42:54
  gives us a chance to hopefully
• 42:55
  reduce the amount of patients
• 42:56
  who need these metastatic treatments
• 42:58
  yeah absolutely
• 42:59
  shifting gears guys sorry
• 43:01
  we're rapid firing through these last few studies
• 43:03
  but um
• 43:03
  let's talk a little about the Tebentafusp plus
• 43:06
  genetics study that
• 43:08
  I think hopefully
• 43:09
  can help patients to interpret their own scans
• 43:11
  and understand their genetics
• 43:13
  go ahead and just summarize the study
• 43:15
  and I'll ask questions as they come up
• 43:17
  yeah so uh
• 43:18
  this this was a
• 43:19
  a clinical and molecular outcome study of uh
• 43:22
  a retrospective cohort of 168 patients
• 43:25
  uh it was conducted in
• 43:26
  in uh France
• 43:27
  and this essentially uh
• 43:29
  was a collection of clinical and genomic data
• 43:31
  of metastatic uveal melanoma patients
• 43:33
  treated between 2018 and 2024 with Tebentafusp
• 43:37
  so this is a a real world essentially
• 43:39
  look at Tebentafusp
• 43:41
  overall rates of response and progression free survival
• 43:44
  and overall survival so among 168 patients
• 43:47
  including
• 43:48
  18 patients that were part of immunocore's
• 43:52
  IMCgp 100-202 Early Access program
• 43:55
  so that they would have gotten Tebentafusp
• 43:57
  before full approval
• 43:59
  Tebentafusp was first line treatment
• 44:00
  83% of those patients uh
• 44:02
  median follow up was 20 months uh
• 44:04
  with progression free survival of 3 months
• 44:05
  and a 20 month overall survival rate with a 67%
• 44:09
  over or uh sorry uh um
• 44:12
  the 20 month overall survival rate was 67%
• 44:14
  and the overall rate of response was uh
• 44:16
  8.9% uh and 46% of patients had stable disease
• 44:22
  so patients with extrahepatic metastasis
• 44:24
  which was very small amount
• 44:25
  as you know with uveal melanoma
• 44:26
  only four in this study uh
• 44:27
  which is consistent with what we know about the disease
• 44:30
  had the best outcomes interestingly
• 44:32
  while those with hepatic disease only
• 44:33
  or hepatic or extrahepatic disease mixed
• 44:36
  had shorter progression free survival um
• 44:39
  and then the study also correlated
• 44:41
  some of the genomic information into this
• 44:43
  so trying to correlate you know
• 44:45
  what we know genomically about tumors
• 44:46
  with some of these outcomes
• 44:48
  and it showed that BAP1 and SF3B1 mutations
• 44:51
  were associated with shorter progression free survival
• 44:54
  uh median five and eight months respectively
• 44:56
  and overall survival uh
• 44:58
  median wasn't reached in the BAP1 group
• 45:01
  and 27 months in the SFB31
• 45:05
  SF3B1 group
• 45:06
  respectively
• 45:08
  um and then uh
• 45:09
  disomy 3 tended to be correlated
• 45:11
  with longer progression free survival of 8 months uh
• 45:13
  and overall survival of 30 months
• 45:15
  versus monosomy 3 uh
• 45:17
  with a progression free survival of 3 months
• 45:19
  and overall survival of 28 months um
• 45:21
  so the findings basically
• 45:23
  is a real world cohort of patients
• 45:24
  that get treated with Tebentafusp
• 45:25
  looking at their overall rates of uh
• 45:28
  response survival
• 45:28
  impression for survival um
• 45:30
  and then some of these stratification groups to
• 45:33
  to try and uh determine if there's any genomic markers
• 45:37
  that are particularly uh
• 45:39
  important in uh determining um
• 45:42
  the outcomes
• 45:43
  okay so from this like
• 45:44
  what should patients especially patients who are
• 45:47
  you know
• 45:47
  entertaining Tebentafusp or Kimmtrak as an option
• 45:49
  what should they know when they hear
• 45:51
  stable disease instead of shrinkage
• 45:53
  like why should that still be kind of like
• 45:55
  I mean like
• 45:56
  why should that still be a good thing I suppose
• 45:59
  when when we think about things
• 46:00
  there's a few things I would mention about this study
• 46:02
  um one is a retrospective study is
• 46:06
  is not as robust as a prospective clinical trial so uh
• 46:09
  the data has limitations
• 46:11
  and then you know
• 46:13
  when we think getting to your question
• 46:14
  when we think about things like stable disease
• 46:17
  and uh
• 46:18
  response stable disease
• 46:20
  meaning
• 46:20
  the tumor staying the same and not getting larger
• 46:22
  or spreading to new spots
• 46:23
  is considered I mean we
• 46:24
  we consider that the treatment working
• 46:26
  so I I think
• 46:27
  you know unfortunately we
• 46:28
  we would love it if we gave a therapy
• 46:30
  and all the tumors everywhere went away
• 46:32
  it was gone but that's
• 46:33
  that's not the case with metastatic disease
• 46:35
  so stable disease
• 46:36
  is something that we would think of
• 46:37
  as a favorable outcome
• 46:39
  OK awesome
• 46:40
  obviously
• 46:41
  definitely consider talking with your local oncologist
• 46:44
  or you know
• 46:44
  if you happen to be close to Matt
• 46:46
  go check him out he's over at the
• 46:47
  the Rhode Island
• 46:49
  uh Providence Clinic right
• 46:50
  Brown University in Providence Rhode Island
• 46:53
  okay yeah um
• 46:54
  like we said he's in the physician finder
• 46:56
  so if you're in the northeast area
• 46:57
  and you need a treating physician
• 46:59
  like definitely
• 47:00
  definitely check out the physician finder
• 47:02
  it's like
• 47:02
  one of my biggest pet peeves
• 47:03
  when patients feel like they have to trial
• 47:05
  to go and just at least like
• 47:07
  establish care um
• 47:08
  because I mean
• 47:09
  I think I think you could acknowledge too that like
• 47:11
  it's pretty common in uveal melanoma for like
• 47:13
  patients to maybe have an established place
• 47:16
  and then to potentially travel elsewhere if a trial
• 47:18
  like necessitates it
• 47:19
  but right
• 47:20
  anyway so I do think it's
• 47:23
  it's important though that like
• 47:24
  I think I've talked about this since the very
• 47:26
  very beginning of doing this podcast is like
• 47:28
  how important it is to have a medical oncologist
• 47:31
  who knows and is up to date about uveal melanoma
• 47:34
  like
• 47:34
  not just your run of the mill medical oncologist who's
• 47:37
  like sure
• 47:38
  like join my patients
• 47:39
  like somebody who specializes in this
• 47:41
  somebody like
• 47:42
  you know like you who's staying in the know about like
• 47:44
  data like this
• 47:45
  okay yeah
• 47:46
  no I
• 47:46
  I think the the
• 47:47
  these have been a very important studies to talk about
• 47:49
  for all of oncology um
• 47:51
  it's getting more and more nuanced and and
• 47:53
  and complicating so um
• 47:54
  I think we we have to keep all of that in mind
• 47:58
  when you're seeking out specialists and
• 47:59
  and second opinions
• 48:00
  and third opinions are never a bad idea
• 48:01
  when you have a disease like this
• 48:02
  so
• 48:03
  yeah for sure
• 48:04
  okay well
• 48:05
  let's chat about this very last one
• 48:07
  and then we will wrap it up for the day
• 48:08
  um but this one was
• 48:09
  I think a Quisinostat
• 48:11
  is that how you say it um
• 48:13
  Quisinostat study
• 48:13
  and it was focused on prevention and palliative care
• 48:16
  I guess can you
• 48:17
  from your standpoint as a medical oncologist
• 48:20
  can you define palliative care
• 48:21
  because I think that it gets really
• 48:22
  really confused and mixed up um with hospice care
• 48:26
  palliative care is
• 48:27
  is sometimes synonymous with supportive care
• 48:29
  and palliative care is something that a lot of patients
• 48:32
  to your point
• 48:32
  they think that
• 48:33
  it means that you're being enrolled in hospice
• 48:35
  which is also in a very under
• 48:36
  are poorly understood program
• 48:38
  but palliative care is really supportive
• 48:41
  so they they help with adjustment to disease
• 48:43
  because we know that um
• 48:44
  these are very very tough things to go through
• 48:47
  getting diagnosed with something like uveal melanoma
• 48:49
  emotionally physically
• 48:50
  spiritually
• 48:52
  and they can provide support there
• 48:54
  pain management is another huge area of what they do
• 48:58
  and just overall symptom management
• 49:00
  so um
• 49:01
  you know
• 49:01
  we've shown time and time again that patients who uh
• 49:05
  have early access to palliative care uh
• 49:07
  tend to uh
• 49:08
  do better overall um
• 49:10
  in terms of their symptom management
• 49:11
  and also they they have longer survival
• 49:13
  so um
• 49:14
  that that
• 49:15
  those are very important things that if
• 49:16
  you know your oncologist wants to uh
• 49:18
  incorporate the the help of a palliative care colleague
• 49:21
  it's a very very um
• 49:23
  you know it it
• 49:23
  it can really really help
• 49:25
  yeah okay
• 49:26
  I think that makes sense and I
• 49:27
  I mean I
• 49:27
  I love that idea um okay
• 49:29
  so let's talk about this Quisinostat prevention trial
• 49:32
  and like
• 49:32
  kind of what was the goal of it
• 49:33
  and
• 49:34
  what ended up being the survival trends that are there
• 49:37
  there was two last abstracts we're gonna talk about
• 49:39
  one is the the phase 2 study of uh
• 49:41
  Quisinostat
• 49:42
  for higher risk of melanoma
• 49:43
  and then the other was
• 49:44
  early integration of palliative care into metastatic
• 49:47
  ok so two separate things sorry
• 49:48
  briefly touch about the palliative care study
• 49:50
  this study randomized in a 1 to 2 fashion in France um
• 49:54
  a control group where palliative care was introduced
• 49:57
  per guidelines and an experimental group
• 49:58
  where palliative care visit
• 50:00
  started the announcement of metastatic disease
• 50:02
  by the oncologist
• 50:03
  and then continued alongside systemic treatment
• 50:06
  for one year
• 50:07
  and then the main objective was
• 50:09
  primary endpoint is to compare psychological needs
• 50:11
  at six months after randomization
• 50:13
  just because uh
• 50:14
  we're running short on time um
• 50:16
  jump to the conclusion we could
• 50:17
  we could revisit it in the future
• 50:18
  but overall
• 50:19
  there were no difference in the primary endpoint
• 50:20
  at six months
• 50:21
  and the further analysis is ongoing
• 50:24
  with a median follow up of 12 months
• 50:25
  uh there is a trend for better overall survival
• 50:28
  in the experimental group
• 50:28
  so I I think the takeaway is that
• 50:31
  while this study has its own nuances
• 50:33
  early intervention of palliative care is is generally
• 50:36
  very favorably thought about
• 50:37
  of these patients
• 50:39
  and it does show a increase overall survival
• 50:41
  so while people think palliative care I'm I'm
• 50:43
  I'm dying now it's not
• 50:44
  not true um
• 50:46
  so
• 50:46
  definitely something to talk to your oncologist about
• 50:48
  and and
• 50:49
  you know understand that a little bit more
• 50:51
  no I love that
• 50:52
  and I think like you said
• 50:53
  like it's just so important to have that discussion
• 50:54
  and to not be afraid of it
• 50:56
  because it really it sounds like it
• 50:58
  it has a much more favorable way of just giving you
• 51:02
  you know
• 51:03
  if you want to live your life well with stage 4 cancer
• 51:05
  like why not actually use all the tools to do that
• 51:07
  that's kind of the way that I would look at it
• 51:09
  right right
• 51:10
  exactly exactly
• 51:12
  okay alright
• 51:13
  well our last study then is the Quisinostat
• 51:15
  let's just like jump in there
• 51:16
  I know it was really pretty um
• 51:18
  pretty short um
• 51:20
  in terms of what was there and what did they study but
• 51:22
  but I know this one is I
• 51:23
  I think still kind of in the midst of continuing
• 51:25
  so um
• 51:26
  what do they know so far
• 51:28
  Quisinostat is basically a
• 51:29
  a study looking at prevention in uveal melanoma
• 51:33
  tumors and for background
• 51:35
  tumors are classified as low risk or high risk
• 51:37
  metastatic categories
• 51:38
  based on their Gene Expression Profile
• 51:41
  uh so this was an open label
• 51:42
  multicenter investigator initiated study
• 51:44
  it's phase 2 study to evaluate the effect of adjuvent
• 51:47
  Quisinostat treatment
• 51:48
  in high risk uveal melanoma patients
• 51:49
  on distant metastasis free survival at 36 months
• 51:52
  this is a trial in progress
• 51:53
  so this is something that's going on
• 51:55
  there's not really much data yet
• 51:56
  but essentially
• 51:57
  they're going to be looking at this as a potential um
• 52:01
  adjuvant treatment
• 52:02
  after definitive therapy in high risk groups
• 52:04
  to try and see if they can reduce the
• 52:06
  the development of metastasis in the liver
• 52:08
  which is one of the more important things
• 52:10
  there's not much to report on in terms of data
• 52:11
  but I think it's something
• 52:12
  we should definitely keep our eyes on
• 52:13
  in terms of whether or not
• 52:15
  there are any early safety concerns with the drug
• 52:18
  and I think we're always away from knowing any of the
• 52:22
  outcomes in terms of distance
• 52:24
  metastasis free survival but hopefully in the future
• 52:27
  we'll have some more information on that
• 52:28
  yeah absolutely
• 52:29
  well we have covered a lot
• 52:30
  you guys so if you've been listening
• 52:32
  and you've been taking notes or like
• 52:33
  hitting pause like
• 52:34
  feel free to come back to this
• 52:35
  listen to it later this will be available and
• 52:38
  and I think you know
• 52:40
  one of the maybe challenging things is like
• 52:42
  even now there's more studies that are coming out
• 52:45
  there's more like
• 52:45
  upcoming clinical trials
• 52:47
  that are starting to open for enrollment
• 52:49
  so just stay tuned like the
• 52:50
  you know the research is definitely making waves
• 52:53
  even though it can feel like sometimes
• 52:55
  it's not moving fast enough
• 52:56
  for those of us
• 52:57
  who are dealing with metastatic disease
• 52:59
  but what do you feel like just kind of to close
• 53:01
  Doctor Hadfield what do you feel like
• 53:02
  patients should take away from this kind of
• 53:04
  overall research wave um
• 53:06
  and the you know
• 53:06
  just the importance of clinical trials
• 53:08
  I think when you think about uveal melanoma
• 53:11
  particularly it's a
• 53:12
  a rare disease
• 53:13
  tapping into an advocacy network
• 53:15
  tapping into a physician finding networks to try and
• 53:18
  you know find specialists is really critical
• 53:20
  there is thankfully
• 53:22
  so many um
• 53:23
  new and exciting therapies that are in development
• 53:26
  but as of now and for the foreseeable future
• 53:29
  a lot of these
• 53:29
  are gonna be in the realm of clinical trials
• 53:31
  so um
• 53:32
  you know if you have questions about clinical trials
• 53:34
  whether or not it's how they're conducted
• 53:36
  what the phases are what the details involving them are
• 53:40
  it's important to talk to your oncologist about
• 53:41
  anytime you're being treated with the disease
• 53:44
  you should really make sure you understand
• 53:46
  what the clinical trial landscape is
• 53:47
  and whether or not
• 53:48
  there may be a trial that's a good fit for you
• 53:49
  because you know
• 53:51
  these really are the most promising therapies
• 53:53
  and that's born out in these results
• 53:54
  that we got from ESMO
• 53:55
  yeah absolutely
• 53:56
  well I mean
• 53:56
  I just remember when the ESMO studies all came out
• 53:59
  and we saw this like we um
• 54:00
  our our clinical um
• 54:03
  I'm trying to our I guess
• 54:04
  our main science person Kevin
• 54:06
  who goes and he like
• 54:07
  observes and and goes to all of these conferences
• 54:10
  and
• 54:10
  kind of brings back the biggest takeaways for patients
• 54:12
  he was so excited after this set of
• 54:14
  of results and this was probably one of the
• 54:17
  the highest level of like
• 54:19
  or the highest quantity of
• 54:20
  studies published around uveal melanoma
• 54:22
  like all at once
• 54:23
  um so I think we were
• 54:24
  we were all really pretty excited about that
• 54:25
  so thank you for helping just add to that excitement
• 54:28
  and break this down for us
• 54:29
  in a little bit more of a patient friendly way
• 54:32
  yeah thank you for taking the time out of your day here
• 54:34
  in the beginning of January
• 54:35
  we're so glad that we're at the beginning of 2026
• 54:38
  and it'll be exciting to see where this year goes
• 54:40
  yeah no absolutely
• 54:42
  I I
• 54:42
  this is exciting data and
• 54:44
  and hopefully
• 54:44
  it means new and better treatment options for
• 54:46
  for patients like yourself
• 54:47
  so thank you for for talking
• 54:48
  yeah of course
• 54:49
  okay so like I mentioned
• 54:50
  throughout this episode
• 54:51
  you guys make sure to check out the show notes
• 54:53
  check out the description
• 54:54
  and please head to our website
• 54:55
  especially if you want to download this PDF
• 54:57
  that has the breakdown of all of these
• 54:59
  you're welcome to print this
• 55:00
  and bring it to your oncologist office
• 55:01
  if you choose um
• 55:02
  just like
• 55:03
  just show them I mean
• 55:04
  I think that's one
• 55:05
  of the things that can be tricky as a patient
• 55:06
  is to kind of embrace that area of
• 55:09
  I can be my own advocate but it really is valuable
• 55:11
  I have not yet met any doctor
• 55:13
  who's had any problem
• 55:14
  with me bringing something to them
• 55:15
  and saying hey
• 55:16
  what about this like
• 55:18
  this is part of the let's think outside the box and
• 55:20
  and work together to figure it out
• 55:22
  absolutely
• 55:24
  okay alright
• 55:25
  well thanks for joining us again
• 55:26
  Doctor Hadfield and I'm just
• 55:27
  a huge thanks to our podcast and YouTube channel
• 55:31
  sponsors Castle Biosciences
• 55:33
  Immunocore Aura Biosciences and Delcath Systems
• 55:36
  we could not do this without you guys
• 55:38
  and without our wonderful volunteers um
• 55:40
  of the physician community
• 55:41
  who just come on and try to keep us up to date
• 55:43
  so thanks Doctor Hadfield
• 55:45
  we look forward to having you back
• 55:47
  thank you so much