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Are We in a Clinical Trial Drought? | The Eye Believe Podcast · The Eye Believe Podcast

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hey everybody welcome back to the Eye Believe podcast
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I'm joined today with Doctor
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Marlana Orloff from Thomas Jefferson
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we are so glad to have you back Doctor
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Orloff thanks for joining us today
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absolutely
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okay so guys today we're talking
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about something that's a little bit um
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maybe a little bit uncertain in the uveal
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melanoma metastatic world
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uh it kind of feels a little bit like
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there's a little bit of a clinical trial drought um so
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Doctor Orloff can you just kind of
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talk to us about like what's going on right now and
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should we be worried
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should we you know where should we be keeping
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our focus as metastatic patients
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yeah um absolutely so I I think you know any cancer any
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disease really that you know relies heavily
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on clinical trials for pushing the field forward um
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it can feel like there's peaks and valleys
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ebbs and flows
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you know you could at some point in time have
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you know a dozen or more
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really great clinical trials all different lines of
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you know therapy previously treated treatment naive
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you know for uveal melanoma specifically
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HLA positive negative and then all of a sudden
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it feels like there's very few
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um and you know it's it's really I think
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right now we're kind of coming
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down off of what I would consider probably a high
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and you know I think a lot of patients
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are kind of asking questions like okay well
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you know what's
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what's out there for me what should I be doing what should I be thinking
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about so I thought we would use this time um
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I have a short presentation just to kind of
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talk about maybe some of the things that have just wrapped up
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um that are kind of no longer available
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right now but then also trials
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that are available and then maybe what's coming down
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the pike okay so I'm gonna share yes let's do this
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so the real question is are we in a clinical trials
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drought so um you know I think
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again um as I mentioned I think for a while
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you know it was raining the rivers were high
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um and now we're feeling kind of as some trials
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have wrapped up and the water has receded
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you know are we are we in a drought
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so as I mentioned I just wanted to start out by kind of
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wrapping up um
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you know or talking about the trials
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that have maybe since wrapped up um
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and you know maybe given a little bit of insight
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about where things are headed so
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I think one of the biggest trials
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that is you know since wrapped up
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um was really a multi prong trial
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you know here I'm showing kind of the study design
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for the randomized trial which was the frontline trial
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for A2 negative patients um looking at uh drugs
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Darovasertib and Crizotinib so that's the PKC
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inhibitor and the met inhibitor
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and these were targeted therapies and if you're
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you know not a stranger to um this podcast
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or you know keeping an eye on things all going in uveal
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melanoma you've
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heard about this trial for a number of years
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perhaps you even participated in it and
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this was the randomized trial
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um that really is an effort to get this drug
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potentially approved so it was
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pure first line A2 negative
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um because the A2 positive patients
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have Tebentafusp
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um versus investigator choice which was widely
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pretty much um immune checkpoint inhibitor therapy
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um and so this trial enrolled very quickly
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um and has since completed um and um
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and you know again hopefully leading
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um to kind of an accelerated type approval
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at the same time this trial was open um
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there was also kind of the earlier
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trial that allowed patients who were previously treated
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and actually even allowed a to positive patients so
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what um what was recently presented um back in October
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was actually the first reported overall uh
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survival of this combination
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as part of kind of that original trial we call OptimUM-01
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again just wanted to kind of highlight
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cause this is the
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the most data that's out there there will be
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more data coming out for OptimUM-02
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which was the randomized trial that just finished
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but um you know that will be
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a little bit more post ASCO
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so you know again this is kind of um some pretty um uh
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you know uh high level data this is part of the
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the presentation at SMR but
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you know again here you can see that these drugs
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are really targeting that mutation
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that we commonly see in uveal melanoma the GNAQ GNA11
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and the important thing with this trial was that
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it um it was really
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the trial that also established dose
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of the Darovasertib 300 mg BID plus
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Crizotinib 200 mg BID
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and so what this trial was really looking at um
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is a subset of patients that were treated
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in that earlier trial
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um and here you can see just in 41 patients
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overall response rate 34% um a lot of patients having
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partial and stable disease and we call a disease
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control rate of about 90% so that's really having a
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response or stable disease um and duration of
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response you can see there about nine months
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so again this was very positive data
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you know I think we're hoping
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that the subsequent randomized data um will will um
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fully show this some of that data has
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since been released and looks pretty good
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um but again so you know again this trial wrapping up
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right now a lot of patients are like okay great
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the data is fantastic can I get these drugs
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and the truth is not right now so you know with the randomized
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trial wrapped up
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the O1 kind of backfill cohort trial closed um
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you know these drugs are not really available
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yet for patients with metastatic disease
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so we're kind of in this weird in between period
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which we've experienced before even with Tebentafusp
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where we have a positive trial
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drug looks you know potentially
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good but we're still waiting potentially
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now for approval to be able to get patients
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access to it so my hope is just that it's coming
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so another trial um that you know wasn't necessarily
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kind of a global trial
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um but something that did wrap up um was the Chopin
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trials this was kind of the long awaited
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read out of the the comparison again randomized of
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PHP alone versus kind of PHP sandwiched with Ipi Nivo
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and there were early signs
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that this was potentially a really um uh
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important or effective approach
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with just a few patients
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uh treated and presented a number of years ago
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but this was the first randomized trial and you can see good numbers
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in the arms 38 in each arm and what we're seeing
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here is that the combination group so again that
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that sandwich approach had a much improved PFS
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one year PFS and median PFS
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um as well as an improved um potentially
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two year overall survival one year overall survival
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still a bit similar with an improved median OS
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so again this is single center um
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it hasn't necessarily been replicated kind of globally
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but it was randomized
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and the different thing about this data
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coming out that looks good and positive
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and potentially promising compared to the Daro/Criz
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is that because
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PHP and Ipi Nivo are already approved therapies
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it's not like we're in this holding pattern
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until this necessarily gets approved
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so a lot of patients if they're eligible for
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PHP if they're eligible for Ipi Nivo
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are now getting we call the Chopin
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kind of style approach or the Chopin combo
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as kind of standard of care now so you know
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again even though this is the trial is wrapped up
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um these are therapies that are an option for patients
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um
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and though this is just a bit more about the overall
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response um and the safety
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so another trial that was enrolling
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uh pretty quickly here um
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uh in especially in the US was the
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uh trial of Roginolisib um or Rogie for short
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uh which is a PI3 kinase inhibitor um the trial
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was patients who were previously
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treated so it really met
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an unmet need for us in the space
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whereas patients could have
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you know could have progressed on prior liver directed
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could have progressed
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on prior Tebe could have progressed on prior Daro/Criz
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and then
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all they had to have had to get on this trial was prior
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um essentially immunotherapy
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exposure cause the thought is that this drug
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Roginolisib can kind of like reinvigorate
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the immune system that might have already seen um
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in immunotherapy
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and this was randomized to essentially anything
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you could have randomized to what we called
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Investigator choice which could have included
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you know best alternative care
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which could have been just supportive therapy
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um other immunotherapies
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um potentially even liver directed therapy
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um and this trial has since now closed um so
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the the difference about this trial
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instead of the Daro/Criz
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trial was that this trial wasn't necessarily powered
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to to get approval safe for Roginolisib in it
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um this was really more of like a signal seeking
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like do we move forward
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um to try to you know do a larger study to to try to
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you know see what happens next um but we'll see um
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you know sometimes even small trials
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can get the attention um and get things um
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approved and what not but I think this
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we'll wait to see this data
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um this data may then launch into another trial um
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that that may bring you know this drug as as an option
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um and this is just the way that the trial was designed
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so you know
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again I think even though some of these kind of
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important fully enroll you know trials
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that were you know enrolling a lot of patients
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have closed um
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you know there are still options
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and I and I would argue to say that if we're feeling
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like we're in a bit of a drought
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that I think the rain is coming
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um and so let's see oh oh my
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sorry my animation didn't work as as I planned
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there but there we go um
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but it is it is I think the rain is is coming so
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you know again I think also when when
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we're feeling like we might be in a clinical trials
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drought
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you know we do still have plenty of standard of care options
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you know obviously
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we're always still looking for kind of the next best
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but you know
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patients who are HLA positive there's tebentafusp
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there's all the liver directed therapies
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there's things like ablation and Histotripsy
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there's radiation
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there's still the immune checkpoint inhibitors
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so there are still a variety of standard of care
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options
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there are also trials that are still open
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so this is the RP2 plus Nivo trial
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which is a randomized trial of a a an approach
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that I've talked about I think on here actually before
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which is a modified virus that's injected
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directly into the tumor and this is in combination
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with Nivo and this is essentially verse Ipi Nivo
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and so um this trial really came out of prior uh
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experience with this in in uveal
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melanoma small numbers of patients
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but here you can see there's patients who had
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their tumors injected
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that responded and even tumors that weren't injected
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um in the liver that responded
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um and these were also patients in that
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group that actually
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progressed on prior immunotherapy but
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this trial um that again is still open and rolling
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is um metastatic uveal
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um you can't have had prior immune checkpoint
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um so you can't have had prior Ipi Nivo um or Opdualag
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or anything like that because that's basically
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what the trial is randomized to
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so um and you can't have had more than one prior line
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so essentially what this allows is prior Tebentafusp
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or prior really Daro/Criz um
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the only other thing that I would say though that's a little kind of unique
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um about this trial um is that there are some cut offs
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when it comes to liver function um as well as number of
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kind of organ sites outside the liver
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so there can't be more than kind of two other
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organ systems affected
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by the melanoma outside the liver
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um so there there is a little bit of nuance um
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and oh and there's also um a limit on percent liver
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involvement can't have more than half the liver
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involved so there is a bit more
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kind of nuance on this trial to be eligible
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um but you know again someone coming right up
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right off a Tebe um
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you know certainly this this could be an option
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but say you've previously had the Chopin trial
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you would or the Chopin approach
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you would not be eligible
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one because you've now had also
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low bar full liver directed
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therapy which is not allowed necessarily
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um and you've also previously had Ipi Nivo
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so again just you know you folks
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have probably heard me talk about this before I think
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when you start at square one it's always
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important to kind of understand what option A B C D
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might be
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so that if you're really hoping to do option C
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you make sure that option A or B won't then exclude C
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um and so I think that's something that you really have to think about if you're considering
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the RP2 trial just because of some of those um
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inclusion exclusion criteria
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um the other trial that is enrolling um
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though I think because of the nature of being a phase
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1 study
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it's a little bit tricky to to get maybe a slot
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and and I think the future of subsequent studies
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is still a little TBD
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but but hoping that they'll be a subsequent
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phase 2 study is the NovelWise or NBM-BMX
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so this is a type of HDAC inhibitor
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um HDAC8 specifically
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single agent um in the phase 1 obviously
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still trying to explore dose
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um and then like most phase ones
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this is nice because there's no really limit to prior
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therapy so can have previously
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been treated with a variety of different things
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um again this is open few sites in the US
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but um only a few slots
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normally there's only like three or so slots
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per dose cohort can take a little while to enroll
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um but there hopefully will be a future
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trial that will then enroll more patients
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um and then I just put this slide
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up here this happens to be our kind of
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institutional Tebentafusp plus trial
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um this one we're um you know um
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exploring the combination of Tebentafusp and liver directed
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therapy specifically immune embolization up front
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um but there's actually a lot of sites um around
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us and abroad that are looking at Tebentafusp plus
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so whether that's Tebentafusp
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plus something like a cytokine like IL-2 or
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Tebentafusp
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plus another type of liver directed therapy such as PHP
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so kind of now a combination of therapies
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that we already have approved a standard of care
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um and I would definitely encourage folks
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um you know to to kind of investigate those trials
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um to see if they're
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um if they're eligible because sometimes
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it's nice to kind of do this combination or
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sequence approach um uh
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because I think there you know as the Chopin
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trial has showed us you know there's possible
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synergy between these systemic and liver directed
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therapies
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so I think um definitely
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stay tuned to discussion post ASCO
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I think that maybe where some of the
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some of the rain is in the forecast um
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so I think there's gonna be a number of trials
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being discussed at ASCO
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um many smaller trials that are gonna
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have um maybe abstracts presented
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may lend themselves to larger trials
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in the upcoming months this includes things like TIL
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things like that radio
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uh kind of ligand therapy MC1R
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um other combinations
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certainly treatment in the adjuvant and neo adjuvant
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setting um other abstracts
15:24
if you've already perused um what's going to
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potentially happen at ASCO also some uh
15:29
interesting things about modes of surveillance
15:31
um but you know I would still say um
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and I and I I know the community feels
15:36
this that there's still a large unmet need for these
15:38
two plus you know second line plus trials right
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you've had a prior liver directed
15:43
you've had a prior Tebe
15:44
now what you've had prior Daro/Criz
15:47
maybe you also have Tebe now what um you know um
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you know I think when it comes to trials right now
15:54
we're definitely
15:55
you know not you know there's not a whole lot um
15:58
for patients who've had a lot of prior therapy
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and while we have some effective therapies
16:03
that are really improving patients um survival I think
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um you know none of these yet
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you know for the most part are
16:11
are really a home run right we're not we're not curing
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you know um
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folks yet so I think really having something
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you know beyond that second line
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for patients who are still feeling well
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liver functions good you know still a
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really large unmet need and and I know that's where
16:27
a lot of us um researchers and and um
16:32
physicians are really trying to you know push
16:35
um to get to get options for patients
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so oh there's my animation again
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um so with that I will end my presentation
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Dr. Orloff thank you so much like I feel like this helps
16:47
kind of put things in perspective and
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um and really just shows like a what happened
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right we've got trials that they didn't close
16:54
because they're not effective they closed for gathering
16:57
data and to the be able to move to the next step
16:59
and that's huge in our community
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because that's the only way we get something like Tebentafusp
17:04
or the Hepzato PHP approach like
17:06
that's the only way that those things happen is when the trial
17:09
closes and then we get the data that
17:11
that says hey let's get approved
17:14
yeah yeah and I know I I feel like you know
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though that waiting period you know um
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can feel like forever
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right if if you're a patient waiting for something
17:24
like that waiting period
17:25
like I get it I I wish I could push a you know fast
17:29
fast forward button but um but unfortunately
17:32
it it takes a bit
17:33
so we are we are in that there now though yeah
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so while we are in this kind of waiting period you mentioned
17:40
focusing on those standard of care options
17:42
so let's just kind of run through
17:43
just like discuss those um outside of trials
17:47
which I know you mentioned
17:48
the couple of enrolling trials that are still there
17:51
uh huh
17:53
what do we have to focus on if we're in the metastatic
17:55
community cause I know like myself I'm metastatic
17:57
I know there's plenty of people who might be listening
17:59
who you guys are also metastatic
18:01
so where should we be keeping our focus
18:03
in the standard of care
18:05
so I
18:05
I think some of it's gonna depend on what you've already had
18:08
um you know um so if
18:10
if you've not previously had Ipi Nivo for instance
18:14
um and you're a candidate for liver directed therapy um
18:17
then certainly exploring you know the Chopin
18:20
style approach um which was that kind of PHP
18:23
Ipi Nivo sandwich
18:25
sequence um you know I think is definitely something
18:28
um the patient should consider
18:30
I do think a little bit of the tricky
18:32
part is if you really look at the trial
18:34
it was essentially in patients
18:35
who were previously untreated
18:37
so I think there is some uncertainty
18:39
in knowing how the data
18:41
how someone's gonna benefit from that approach
18:44
say if they've already had Tebentafusp
18:46
or they've already had Daro/Criz
18:48
and Tebentafusp or they've already had Y90 um
18:51
you know cause I think the
18:52
the trial was more so in kind of a patient
18:54
population who had not
18:56
significant had significant treatment before
18:59
um but but I think it's still worth
19:01
worth a shot you know specifically if you're
19:03
eligible for
19:04
PHP and previously had not had checkpoint
19:06
I think what we really don't know is if you did have checkpoint
19:09
you know is it worth it to combine the checkpoint
19:11
again with PHP right say you were
19:13
on the Daro/Criz trial or even the RP2 trial
19:16
and you got randomized to the Ipi Nivo
19:17
arm and you had a couple of doses and maybe progressed
19:20
is it worth it to try the Ipi Nivo again with the
19:23
PHP if you're gonna go down that road I think we don't know that
19:25
um so yeah
19:28
from a I guess the place
19:30
the place that I think of the Chopin approach from like
19:34
just the theory
19:35
maybe behind it that obviously we can't prove
19:38
for sure but like the theory
19:39
behind it that I like to kind of live in as a patient
19:42
um is this idea that
19:44
Hepzato or like the PHP helps to sort of wake up the immune system
19:50
to what's there becasue dying cells become more available to the immune system
19:54
and then in theory it could make the immune therapy a little bit more likely to pick up on it
20:00
yeah yeah so for exactly or it somehow clears
20:03
out the bad immune
20:04
cells so there's these things called
20:06
Tregs that maybe live in the liver yeah exactly so
20:09
so in that case if we kind of just go on that theory
20:12
then yeah maybe reintroducing Ipi Nivo after PHP
20:15
may have more benefit
20:17
than you know somehow the PHP resensitizing someone
20:20
um you know to to to the immunotherapy so
20:23
you know I think it's a harder probably conversation
20:25
if you had tox with that Ipi Nivo
20:27
back you know whenever you got it but but you know
20:29
again that's you know that's a conversation to to have
20:32
so what's your opinion generally
20:34
like just as an oncologist
20:36
who's been in this space for a long time
20:38
um what's your opinion on Ipi Nivo
20:39
cause I feel like in the community
20:41
there's kind of this general myth
20:43
that's existed that like oh Ipi Nivo is terrible
20:46
we never wanna do Ipi Nivo
20:47
um but I've talked to oncologists who are like well
20:50
we can manage the side effects whats your judgment call
20:55
yeah so I you know I I wish we had something
20:57
better I mean listen Ipi Nivo in skin melanoma
21:00
like you know obviously
21:02
it's been amazing for um for patients
21:06
I think in uveal you know I think there's real sometimes
21:11
hesitation just because we know the response
21:13
rates aren't fantastic but it still has all the tox
21:16
um and the tox can become life threatening
21:19
the tox can prevent you from getting other things
21:21
but I think the hard part is
21:23
that there are some patients who respond
21:25
um and we don't
21:27
we have some clues on maybe who that could be um
21:30
but generally I don't think we we are fairly confident
21:33
in predicting who's gonna actually get a response
21:36
from from Ipi Nivo
21:37
but there's definitely patients who do
21:39
so if if you got
21:40
you know if you don't have any other better option
21:43
and certainly if someone's progressing with disease
21:45
outside the liver and you
21:47
you know for which you know you can't do liver directed
21:48
therapy
21:50
you know then I think Ipi Nivo is an is an option
21:53
um because there are some patients who do respond
21:56
and and yes we can manage the side effects
21:59
though sometimes obviously they're not very fun
22:01
um and some can be pretty hard to manage um
22:05
but um but yeah I I I don't love it I I
22:10
wish it was better I wish you know it was
22:12
it wasn't as toxic I wish it had a bit better of a
22:14
response rate but we definitely do use it um
22:18
you know I would say with all of the clinical trials
22:21
that we have with Ipi Nivo as the comparator arm
22:23
or now with the Chopin style approach
22:26
you know I would try to if you're gonna expose yourself
22:29
Ipi Nivo I would do so kind of either in a trial setting
22:33
you know or in the PHP combo setting
22:35
so you're not doing it just to do it you know so
22:38
it's it's sometimes unfortunate you know if a patient
22:41
has already had Ipi Nivo as first line just because
22:44
then they come to us and they're not eligible for either the RP2 trial
22:48
or now you're hesitant to do the PHP
22:51
Ipi Nivo thing or when Daro/Criz
22:53
was available then they're not eligible for that so
22:56
you know again kind of and
22:58
you know it's hard to go backwards
22:59
but certainly if you're a patient with new diagnosis
23:02
you know just at least having consultation somewhere
23:06
to make sure that there's nothing else you should be doing
23:09
first line as to not you know burn burn a bridge so
23:13
what about liver directed therapies outside of PHP
23:18
where do you feel like those live in this kind of space of this waiting
23:21
you know between all the trials and what's gonna be coming
23:24
yeah so you know obviously a lot of you folks
23:27
know at our
23:28
institution we still do a lot of liver directed therapy
23:31
um whether
23:31
whether it's immuno embolization
23:33
either on that trial with Tebentafusp or by itself
23:36
um chemo embolization
23:39
um so that's chemotherapy but embolizing
23:41
so not the perfusion like in PHP
23:44
um Y90 radio embolization still an option
23:48
so these are definitely all still options um
23:50
certainly for patients
23:51
with liver dominant liver only liver dominant disease
23:54
um patients who
23:56
maybe there's not a clinical trial that makes sense
23:58
patients who don't want a systemic
24:00
therapy for you know whatever reason you know or
24:04
certainly the chemo embo
24:06
I would say the place that we're using it a lot is
24:09
if even if someone does have Extrahepatic disease
24:12
if someone's coming in with
24:14
pretty bulky or rapidly growing tumors in the liver
24:18
and you know
24:20
um maybe it's gonna take a minute to get PHP set up
24:23
um or Ipi Nivo set up or they're not eligible for PHP
24:27
you know we can use chemo embo
24:29
um because we can do that pretty quickly like yeah
24:32
you know normally
24:32
we see a patient we can do within a week or so
24:35
um it's kind of a stop gap to try to kind of hold
24:38
hold things so then you have a minute to breathe
24:40
and then kind of say okay
24:41
is there a trial is there another approach
24:44
we want to be taken or time to get things set up yeah
24:48
are you I mean I guess it really just depends
24:51
on where somebody is in the metastatic
24:53
journey um but like
24:56
if you have somebody who shows up and they've got
24:58
you know new metastatic diagnosis
25:00
maybe one or two liver lesions
25:01
like are you looking at like IE or CE
25:04
more or are you looking more at like maybe ablation
25:07
or surgical like where do you feel like those other options fit in
25:10
yes so I I think so you're right so I think a patient
25:12
who presents with very limited disease um
25:15
you know I think in some ways these are sometimes
25:17
the harder patients
25:17
right cause maybe you have all the options on the table
25:20
you know maybe RP2's on the table
25:21
PHP and Ipi Nivo is on the table immunoembos on the table
25:25
check if it's just one or two tumors
25:26
yeah things like ablation could be on the table
25:29
um so you know in those cases
25:31
you know we kind of hash it all out right so
25:34
again you've um
25:36
you've probably heard me talk about this but kind of my decision
25:38
tree so you know knowing HLA so again patients
25:42
who have very limited disease who are A2 positive
25:45
certainly things like Tebentafusp um
25:47
on a clinical trial or by itself
25:49
um you know can make sense um
25:53
we would normally do immuno
25:54
embo if we were gonna reach for a liver directed
25:56
therapy
25:56
if we're really just talking about one or two tumors
25:58
very limited disease
26:00
you know the the way that we think about ablation
26:03
or histotripsy rarely surgery um
26:07
is is patients who've really declared themselves
26:10
as having
26:10
truly slow growing kind of oligometastatic disease so
26:14
we like to see maybe a couple MRIs showing
26:18
no other tumors because you don't want to put somebody
26:20
through an ablation or Histotripsy
26:22
and then your scan a month or two later
26:25
there's five more tumors so you know often
26:28
if we have a patient who maybe we've been following
26:30
this like 7 millimeter thing
26:32
and then it's 8 millimeters then we biopsy it
26:35
then we get another scan and it's 1.2 cm
26:39
you know we'll we will ablate that
26:42
it still doesn't have friends we will ablate
26:44
that I think we feel very comfortable ablating
26:46
something like that um
26:48
you know the thing though to
26:49
remember is that things like ablation
26:51
surgery and Histotripsy
26:53
depending there are some trials
26:55
that consider that a line of therapy um and so
26:59
you know do you want to do this you know
27:02
potentially short term
27:05
you know very directed therapy
27:06
that could buy you a period of time of no treatment
27:10
um or
27:11
do you just wanna go right onto potentially a trial or
27:13
another treatment because
27:16
you know if you do the ablation then you can't so
27:19
again these are all things that certainly come up in um
27:22
come up in conversation and
27:24
and you always wish you have a crystal ball
27:26
um but I haven't found a crystal ball
27:28
yet so you kind of you know use your experience
27:31
your judgment discussion with the patients
27:34
you know and understanding of hopefully
27:35
what's out there what's to come
27:37
um you know to to hopefully make the right choice
27:41
yeah well and I wanted to ask you you mentioned
27:43
like you know that we have this big discussion
27:45
um do you feel like you have that discussion
27:47
like first and foremost just mostly with the patient
27:51
or do you guys have at Jefferson
27:52
like I just know that some some areas
27:54
like some of the regional centers
27:56
like the bigger centers they have like a tumor board
27:58
or they have like a large group of doctors
28:00
that they all get together and they look at the scans
28:02
and they go like oh my gosh what are we looking at here
28:04
how do you guys typically approach a new metastatic or a progressing matastatic patient
28:09
yeah um so we have a tumor board every Monday morning
28:14
where we review all the patients
28:16
that we're gonna see in clinic that day um
28:18
as well as then probably 20 or 30 or more um
28:22
other patients who were following their scans um
28:25
and certainly if it's a new patient referred
28:27
to us or it's a patient that has new progression
28:30
exactly you know um
28:31
our tumor boards really radiology driven so
28:34
you know MRIs of livers cat scans
28:37
you know up on the screen um IRs present
28:40
met med oncs present sometimes radiation oncology is
28:43
present our research coordinators are present
28:45
and we hash it out um
28:47
and sometimes there's you know um you know uh
28:51
agreement between all parties um
28:53
you know and sometimes people have different thoughts
28:56
um and you know ultimately we take that conversation to
29:01
to the patient so then we also see patients together so
29:04
then med onc and IR
29:05
will actually see patients
29:06
together in the same room at the same time
29:08
that same day if it's patient being seen that day
29:11
and we'll kind of rehash what our group discussed
29:14
and you know often times we come out of that meeting
29:16
saying like okay I think we're gonna recommend A
29:20
you know if the patients feeling
29:22
a certain way about it you know B or C are totally
29:24
other you know also reasonable
29:26
or we only recommend A and
29:29
these are the reasons why we wouldn't do B or C
29:31
and essentially then we take that conversation
29:34
um into clinic with the patients and and go from there
29:37
yeah no I love it I think it's so it's so
29:40
interesting to hear like this kind of it's
29:42
such a collaborative approach
29:43
and I think that it allows room for
29:47
those kind of out of the box options to become
29:49
part of the discussion
29:51
or just the creativity of medical care
29:54
especially in uveal melanoma like I feel like that's
29:57
it's one of the challenges
29:58
but it's also I think one of the cool things that we get to witness
30:01
that you guys do as doctors so I love that
30:04
um what about Kimmtrak
30:06
I know like we just got some data
30:08
about Kimmtrak and that's obviously
30:09
only for HLA-A02:01 positive patients um but
30:13
where do you I mean where do you live now on Kimmtrak
30:16
now that we've got a little bit more of that overall survival
30:18
data to go on
30:20
yeah so I I so yeah so for for those uh
30:23
listening that may not know all the data
30:24
but you know so the original trial
30:26
read out then there was a three year overall
30:28
overall survival follow up and then most recently
30:31
I think at AACR um
30:32
there's the five year overall survival follow up and
30:35
and I think it's pretty similar to what we've been experiencing
30:38
you know now that we've been using the drug for a while
30:41
um
30:41
you know there does seems to be a subset of patients
30:44
who just have a very prolonged
30:47
you know benefit from the drug and and survival um
30:50
you know I think what what you kind of see
30:52
kind of in that group are patients
30:54
who've either had prior Tebe
30:55
and are now on something else and still
30:57
having good survival
30:58
or there's actually patients that are still on Tebe
31:00
for just a really long time um
31:03
you know um we've certainly had patients
31:05
who've been on now 5, 6+ years
31:08
um you know on weekly Tebentafusp therapy
31:12
some of them have gotten
31:13
other things sprinkled in over time so I think that is the nice thing about Tebe
31:17
um is that because there's so few side effects
31:20
kind of beyond those first um few doses
31:23
uh you know if someone maybe has a mixed response
31:26
you know a couple years in or something
31:28
new pop up you can radiate it you can ablate it um
31:32
you can do liver directed therapy
31:34
um and you can kind of keep Tebe on
31:36
um in in the background um so yeah I
31:39
again I think going back to the you know early days of
31:42
of Tebe
31:43
you know obviously it was a huge deal to have a drug
31:46
um approved um you know I think we were
31:50
you know we were hopeful
31:51
maybe was gonna have more of a response
31:53
rate but it seems like even without having that
31:55
you know you know big
31:57
response rate up front there's patients who clearly
31:59
continue to derive benefit um so we still
32:02
use a lot of it either by itself or like I said in combination
32:06
um again only for the A2 positive patients
32:09
um but it's a definitely certainly something
32:12
um that we use and again to just um let everybody
32:15
know that if they're thinking about Tebentafusp
32:18
you know to potentially look
32:19
around or ask about these trials that are popping up
32:22
in a couple places
32:23
where it's kind of Tebe plus something
32:25
um because I think that's potentially gonna
32:27
move the needle um a little more forward
32:30
oh I love that
32:31
um okay well well overall I feel like we've covered
32:34
obviously we've covered a lot
32:35
you guys who are listening
32:36
I know we covered a lot so please feel free
32:38
go back and I I should have said this at the beginning
32:40
but if you've been tuning in on the podcast
32:42
and you haven't
32:42
actually been able to like watch the slides
32:45
head over to the YouTube channel
32:46
because we do have the slides
32:47
up on the YouTube channel uh but like this has been
32:51
really helpful
32:52
just to break it down and to kind of see
32:54
the benefit of where we're at right now in the uveal
32:57
space um and I think overall my takeaway here is that
33:00
even with standard of care
33:01
like one of the big benefits
33:02
that we always talk about is that this gives us some more time
33:05
right using standard of care options
33:07
is going to give metastatic patients time and
33:10
time means time for the rain to fall as you said
33:14
yes I feel like we need to like insert
33:15
the Hilary Duff song or whatever but um but yes
33:19
well a lot there's a lot I think there's a Lady
33:21
Gaga song about rain but yeah no I I I feel it um
33:25
yeah I I feel it um I know you know patients are
33:28
you know in need of
33:30
more things um and just to know that
33:32
we're working on it
33:33
um and like I said I would I would tune in post ASCO
33:36
um you know for potentially some uh
33:38
some new things coming down the pike
33:40
okay so post ASCO
33:42
that's where you think we should kind of keep our focus
33:44
going into the summer and these research
33:46
obviously we've had AACR just happened
33:48
so we've got AACR that just happened
33:51
and just you know keep that in mind
33:53
that as we go into the summer we here at A Cure In Sight
33:56
we've got the Eye On Research
33:57
convention that we will do it's just that like
33:59
seminar that's virtual
34:01
and we're gonna kind of pull together all the
34:03
important pieces from AACR and ASCO of course coming up at the end of the month
34:07
in May and June so theres obviously gonna be some announcements and some data
34:13
and so keep an eye out for that literally in some cases
34:18
I feel like that's my token joke I have one eye so then I'm like oh I'm gonna keep an eye out
34:22
I'm like oh wait the only one I have
34:26
but yeah like I think it is a Hilary Duff song the let the rain fall I'm coming
34:32
yep I lover her music I grew up listenig to all of her music and I'm going to see her in concert
34:37
yeah she's back so excited
34:41
but thank you guys for listening thanks for tuning in
34:43
if you're one of our subscribers
34:45
on our YouTube channel or the podcast
34:46
we couldn't do this without our listeners so make sure to just drop in the comments
34:50
if you have questions tell us a little about your story and definitely reach out
34:53
if you have big questions to Contact@ACureInSight.org
34:56
and we'll make sure to connect you with um whether it's through our physician finder
35:00
with doctors close to you that you can get opinions from or just to
35:03
you know help make sure we can get your questions answered
35:07
and let's see last and foremost or last lastly
35:11
lastly, we're gonna just wrap with thanking our sponsors
35:14
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35:17
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35:28
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35:30
And then I guess most importantly Dr. Orloff
35:32
we just gotta thank you for being here and for
35:34
just I feel like you always do such a good job
35:36
of like putting things out there in a really clear
35:38
concise way that I feel like just keeps us focused on the right things
35:43
so thank you for being here
35:45
absolutely
35:47
alright you guys we will see you next time
35:49
make sure to subscribe and we will talk to you later
35:51
bye