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Combining chemotherapy and immunotherapy for first line biliary tract cancer
K. Kelley
Thursday, Feb. 29, 2024 · 3:05 p.m. · 35m 18s
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um my name is katie kelly and good morning from california actually
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um today i had the privilege is speaking on a relatively new
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advance entirely retract cancer which is the combination of chemotherapy and it you
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know there'd be in the first line context here my disclosures actually related
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to conductive multiple clinical trials to his that i'd like to you today
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first go over the background of chemotherapy evaluate check
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answers not biologic rationale for combining within minutes there be
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and then go through our concertina their opinions there'd be combination beginning with early phase data
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and then going into two criminal case three trials to has landed you know nine six x.
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and tell him further into tears seven grip uncorrelated analyses as at least what exists so far
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and then hopefully look to the future for like the next to
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beginning with a background in biology and versus south of a bit better
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than other that's stupid acronyms because as you all know that we're
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a check answers are highly complex too much types of multiple cell works
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so overall user and common timbers that rising
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incidence worldwide around two per hundred thousand over all
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that much higher answer because the world including japan is medium size eight or nine hundred thousand people
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and the anatomy of billy a check answers is quite heterogeneous and this is where we get to that also that's it alright
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we're gallbladder cancers or g. e. c. and in a gallbladder portion of the ha
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and we have enjoyed going to carson as arising from this now into
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a panic and material bile ducts looked in the letter i. c. c.
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and timbers rated function of the packed out to the common bile ducts and up until the cystic debt
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i refer to stereo trailer or highly by less or the old uh and i'm asking two murders
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and just still to take after the sister just basic that down to that and had to pay greasy hair
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just allowed out or and this'll bile that cancer is
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an together very highly and just account for extra panic
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went across america t. c. c. which is what the several commonly used in clinical trials is caught
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and beyond this enormous in now and it's comic
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heterogeneity here check answers also very heterogeneous geology and biology
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so there cause i variety is very different types of the underlined letter injury in a
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large proportion of patients these can include some of the same as factors is h. c. c.
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including hepatitis b. c. virus or alcohol on
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uniquely to billy a check answers hook infection that
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really irritates or as the relatively thailand in southeast asia
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countries can also cause chronic inflammation in meeting to
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teenage damage a trance right malignant transformation every time
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uh the scores on the horizon in believe most parts
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the world is now starting river crossing underlying injury in
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generation mutations and i have had a great command and that really
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irritates so in addition to h. t. c. that either is perhaps
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uh we think one of the causes of this rising incidence
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of internal panic roger carson r. i. c. c. in particular
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i'm just i know that in most cases are still it it ha we don't know why most patients get until you're a
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check answers and so i went ahead and handwriting using complex anatomy
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and physiology turns out that the genetics in my current byron it's
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uh the summers are also highly heterogeneous injured in some cases link
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to their yard your hand and you know there's not so clearly
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so so in terms of working with their the um triple a.
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checking answers is historically been rare cancers that our much level one evidence
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really the first level and evidence um arose from the uh to the trial cut eighty c. o. two
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which combines genocide audiences tightening compared to genocide it being alone
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in the first line and setting for advanced really a check answers
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this station to survival improvement with survival eleven point seven for
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the combination in a median are also that i should say
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versus eight point man for genocide in along with the captain liar curves shown here
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under stars race we're i'm twenty six percent with combination versus fifteen percent version sided
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being alone and i include that just isn't benchmark for what we should expect region says
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and if we look at the foresight we can see the most common
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goal and seven groups uh earlier check answer showed benefits additional system um
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improved overall survival across and most clinically relevant subgroups stage i'm sending pulses
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slammed became the standard regiment her the easier to travel around two thousand
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ten that have been few other first line trials on but any positive
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results hip until recent years and the first in and acts as a
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trial after easier to with and it's super tramp combining genocide in this
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time and a third set a toxic agent the floor pretty nice one
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and this is conducted exclusively in japan and which is why we and i don't see as much of it
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but we don't have this agent written united states or europe and it's another why they use regimen outside of japan
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but the city to show improvement in the media in a survival um which is the primary endpoint thirteen
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point five verses twelve point six months though i'm
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not strongly positive but it was a president cousins study
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um p. s. in response we're also higher with the triplets but so were great
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three events including diary estimate tyson rash another important and recent study but looking at it
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should live content as you know there are you taking genocide it's it's time adding better
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tax seen nah the tassel was the a.
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e. us intergroup steady score of eighteen fifteen
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and this study i'm randomised patients to standard genocide interest this time
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versus the triplets inside of me just fine and patted tassel based
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on a base to do you know what that to do and renovation
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and unfortunately the study do not show significant improvement in overall
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survival um it was a negative studies are the primary endpoint
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um there was a cheap trend towards higher objective response rate but it was not significant
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and again there was actually a pretty easy meaningful in crease in great
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three adverse events basically those are related to milo suppression of the triple agent
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so this management is not moving for is the um isn't
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it true reminisced enough person setting owing to no significant improvement
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in efficacy and heritage chassis so to summarise what we have
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with first nineteen of their data alone in earlier check answer
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the germs anything assist ham combination it she's indian overall survival around twelve months
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and a response rate the fifteen to twenty five percent
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range in contemporary studies with the two drug chemotherapy regimen
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having the third agents such as as one or not heart
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attack so can improve objective response rates that has um modest
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impact on overall survival and higher rates of toxicity and the
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median duration over stances limited meaning when people start it tends to
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be a up till six or seven months of benefit and after that patient's progress it is not a long term a
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solution so i mentioned earlier the micro environment clench across um
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is is quite heterogeneous incorrectly to the very young ages in anatomy
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um and here's an interesting study which looks at us the
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sets a major panic kind of person is put into a predominantly
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and it shows that only about ten percent of them are and
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you know janet gratified micro environment the majority of these are called steamers
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and that you don't need excluded or my later or typewriter can their micro environment
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we also another variable rates of markers associated with the mute responsiveness still
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and they're very low rates of t. m. b. heidi steady ensures immediacy of the red two points you in billy
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a tracking answers and and only has two three percent
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of these elephant billy a check answers have my cassette instability
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alright mismatch repair deficiencies overall this is a cold
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steamer type and as expected for calls to try
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the new check when computers as one of their you have some very limited i think i see
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the best example this is the key you know one friday
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trial that'll little bit over a hundred patients who were and
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a majority oh almost ninety nine to a hundred percent of them were mismatch repair proficient or a
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couple of new cases that overall that ninety nine percent were mismatch repair coefficients not tennis i high
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and the objective response rate as a lot less than six percent overall without a huge difference
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according to keep the l. one status and the media progression free survival is only two months
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we see similar results with rubber start it's less than ten percent
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for most other reject any better studies once reveals actually get these
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and it's not all mounted right now so he said
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is encouraging results that the integrated president well tolerated very
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similar rates of immune related adverse events compared to other
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to recite signal access of attack toxicity early warning signals
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so based on this c. but lacking predominant back of striking i think i see the question arises
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when combining he must there be it with the ninja when you'd better improve the chances
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of eliciting an immune response so there are reasons to think they combining immune to any better
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with chemotherapy could augment the immune response and this is the sort of broad category
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of of approach that has been taking in a lot of different timbre types now and
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on high there are right in different ways to chemotherapy can promote immune responses
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so side of toxic agents can elicit growth mandatory
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side trying to change my environment or isn't immune response
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it can trigger an inset infiltration and particularly in the system in our chances regimen
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can cost characters does it take to start that it really encourages a factor sell infiltration
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on chemotherapy he can inhibit regulatory t. cells mileage derive cells that
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could be cruel immune response and again this specific gems i mean
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um chemotherapy can increase to marina jen immunity city
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and and the union antigen presentation touches genocide
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these increase in an easy one expression engine presentation
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so these are all your uncle lace and but some preclinical data you know can you tell
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we need to we inhibitors which even immune response so looking at early
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data have an intermediate have raised with genesis regimen there a host of small
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in a single i've said if they get a little bit of a signal i won't go through all of those this is just one such example
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um that highlights ignorant encouraging signal also combining people now last german says in this
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um small thirty patients study showed a response later and
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thirty six percent which is again much higher than we expect
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um with genesis alone but not out of the range of possibility when you're only dealing with thirty patients
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um but we see this some of them are quite
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and durable again limited follow are signed a single study smalls
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small data set so it can it a little bit of a single that nothing's it to make it sleeping decision
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based on because uh the small size of the study no colour so he um was done that's worth noting which
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was thinking genocide in it's just fine and the value manner
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plus minus the c. tell it for inhibitor travel right now
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increase in size like that again oh i i'll and this is a much larger city
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with a hundred and twenty patients i'm very complicated design in which patients were written were allocated
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um to three different arms either the triplets with a whole
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bunch of by marker collection um or on the a side it
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but forgot combination 'cause there's to me that there isn't this
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was a foreclosure and companies with what it by our market analyses
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or the chances cluster value not treat record or the genesis
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develop engine room of a different for a coke or an
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and so looking at and that by market data from the first quarter
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in particular um actually side as a three course i just mentioned um
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looking to the um initial data from this study um we see um first there
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is a a most nations had a baby graphic regression and i actually had um quite
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remarkable response rates in the study yet to seventy two percent on
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for the bit combinations um with the cab yeah this is
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a locally assassin us to a selected population of of korean patients
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um i think i can carry out with this study is that the
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the response rates much higher than we take steps and for genesis alone
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um and higher than what we meeting of the other combinations that just a novel
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nested you shouldn't thirty six percent response a second is data must be taken up the
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green it's all but certain provided a very strong interesting signal and then looking to the
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buyer marker analyses from the first one particular indecent interesting things to to draw from here
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but when peel an expansion team b. which again has not been very prevalent in
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or to me is usually won't quite across nobody in this study they were not
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predictable response a couple mutations were type perhaps really write nasty under one in seeking
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into a which we know from other data sets as well had worse at times
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and then this is i think that part is most intriguing in terms of mechanism oh one stations started treatments
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those patients whose two murders had higher p. l.
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one expression after an exposure chemotherapy did have better outcomes
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and i'm including survey but yes and understands me
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patients whose two murders on chemotherapy added decrease including alan
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had worse outcomes and so i think this is interesting because it's it's a little bit uh mechanism that
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tomorrow's the interfaces chemotherapy haven't inflammatory response or increase their
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p. l. one seem to do better and supports it minutely
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mildly supports the hypothesis that will it eliciting an immune
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response i i'm making now so that's the relevant early face
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translated my mainstay now turn to the pivotal phase three trials top as
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many kinetic sex and their cell groups so beginning with has until hasn't mine
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um within the alliance multi centre goebbels basically trial it relocations with local events
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are met a static billy ray track answer so intricate extra padded ankle biter
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and all haitians had previously untreated um or mess that disease at a nuisance i
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am and or uh or occurrence after greater than six months requires surgery regiment there be
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issues or minimise one one of the total sample size of six hundred eighty five patients
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two and either devalue mad and plus the genesis schema back down
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or placebo hostage insisting that background an important design point was that aren't based on the
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original it easier to travel this trial elected to require after eighty cycles max number six months
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all patients switch to either me instrument alone without any market now
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or placebo without any working no um and this is a little different thank you know
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nine six six and a little different impact to start in some part of the world
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um which may continue genocide any longer than six months
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in some patients depending on patient factors so again after
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six months patients were around and i were either remain
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undervalued mommy it's or c. domain it's no kinda there be
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on the primary objective was overall survival in secondary objectives were time
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progression free survival objective response re duration the response which i think is
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very important and we knew there'd be studies and then it happened
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you know once addison safety so the primary and when he's an overall
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survival show improvements and with the addition of joe value mothers median
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it twelve point eight months compared to level by five months and harassing
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the can reservation as they're really zero um and as we look at
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the curves we can see that the the the double curved around that
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really shine increase separation of the curve with um with time suggesting perhaps
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that these patients that the eternal booker virtually having it either durable new styles
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um progression free survival is also prolonged and objective response rate is higher with
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the the purple group the addition of devalue map and i can see continue their
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you know potential for ticket durable immune responses we see that patients with objective responses
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and the most and the longer duration of restarts the d. o. r. it's not
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trained here is the duration of restaurants in the purple curve um i'm generally
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not have that much longer duration understands which is what we hope for more than
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enough there he he was quite similar in both arms and that serious oppressor but
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great great we for race just continuation rates were nearly identical without any significance signals
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in in related adverse events and we're also as expected for divine not it's none of their
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period twelve point seven percent in the component versus four point seven percent of pussy go on
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and great three immune related adverse great we're higher quite well we two point four percent so
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can very reassuring secured this is not i mean patients and if we look at some group analyses
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we can see a candidate who almost all these key clinical sell useful actually all that fall
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to the left alive at waist so all relevant subgroup seem to be showing at the some benefits
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within the magnitude and instead of incessantly you to to press um presentation there then
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additional subgroups um according to how do region of the world
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be so it can pretty similar outcomes great asia versus western states
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and and that is that whole shit for extra credit other
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an interim kind of 'cause well to buy an intimate sense site
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um and we i think a ace circle this that's your race
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and nation versus nomination also and we can sell show similar trends
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hello again there is a slightly more significant stand benefit in asian said good night vision in this
00:18:26
study though that's different you know to show you next so based on like consistency yes
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strength of the data and it's easy to get us f. d. a. approved devalue
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map in on september twenty twenty two and since then many other regions the role
00:18:40
have improved approved edition of each divine outage inside in classes time so here's a
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typical case um but speeches from atlanta just to share uh the talk has one
00:18:52
um treatment example so this does that and sixty seven year old
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you had a an extra credit uh either actually and it just kind of course intimate
00:19:03
um and stand hike a recitation eighteen mutation that was not terminus tuner
00:19:10
and and discuss surgery and then an action to keep fighting
00:19:14
with the low ca ninety nine unfortunate but a year later undercurrents of the high c. ninety nine and
00:19:19
turn your carcinoma test dishonest task and here's a couple
00:19:23
little started some lymph node positive body as well and
00:19:26
a biopsy of that carry this caretaker one of these great big ready
00:19:30
went nuts showed confirmed that it was recurrent bladder carcinoma in the caribbean
00:19:34
and so we put in mansions this cluster baum out her topaz mine
00:19:39
um and he did quite well has a mile crashed beginning and then having
00:19:43
complete restarts and no visible to merge the normalisation of c. in eighty nine
00:19:48
um and did quite well and after six months we switched him to me yesterday
00:19:52
i am out on and about seven months later unfortunately progressed on so can we did
00:19:58
not have is terrible uh let me responses that helped but the converse is that he
00:20:02
had a little background a seven month team of three interval without any sign of progression
00:20:07
um and then when we progress economists second lines local trial at which any progress immediately
00:20:13
um and then now isn't there nine for fox impartially having a better fucking restaurant
00:20:17
again but i i do think this that about not as a contributor to this
00:20:21
and king of three and a role for him to turn into the next phase three
00:20:26
travis is that they had the owner being a part of a kinetic six setting which
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it's very similar study to talk has one but with the p. one hundred camber this is not
00:20:36
as the image of peanut butter is set up to right now so
00:20:39
here's the schema thirty nine six six seconds alright eligibility criteria for um
00:20:44
to it yes or local or other sceptical on a primary goal here
00:20:49
check answer no prior systemic there be on and i'm i'm pretty content
00:20:56
pieces are randomised one to one to either controllers map questions this opus
00:21:01
placebo last chance this and the key difference here decided to go just
00:21:05
to press one is that after six months or a cycles of therapy
00:21:09
to investigate inpatient had the option to continue gem siding which most patients did
00:21:15
um and um that was either what john said it last tango in the two
00:21:19
men on or ten sided dice to see go in that devout in the controller
00:21:24
so unlike talk wise after six months that control and continue to jan as did that
00:21:29
and train and in most in most patients in so that doesn't ha comes to some degree
00:21:34
um primary endpoint is overall survival so here's the overall survival the final analysis with a one thousand
00:21:41
sixty nine patients and also this is the largest they switch around issue billiard track answers to take
00:21:48
and we see is sort of in a sustain separation of the curves and
00:21:52
with the green curve groups of of cannibalism national and along survival of the twelve and twenty
00:21:57
format landmarks a little bit of a separation in the correct twenty four months and and it
00:22:02
the harder to tell here 'cause the small numbers and and incomplete follow that become the twenty formant mark
00:22:08
um but again a significant hasn't ratios are twenty three um
00:22:12
and also like this is a significant step in a process study
00:22:15
for improved overall survival now here are the i'm preset specified subgroups
00:22:20
of the final analysis and we again see or most of this
00:22:24
priestess of identical subgroups there's benefits aren't for but handlers mathematician
00:22:30
and this includes asia versus non angel at a slightly and more strong trend was benefit in the non asian
00:22:36
group and the study on like topaz again these various
00:22:39
reinforce it all asia and on occasion patients in regions benefit
00:22:43
um we seen no significant difference bright yellow ones collapsed refer to it as as well i mean
00:22:49
i like that earlier and then we see in the interpreting who are the best in this group study there was less
00:22:55
than if they are less clear cut difference writer product or gallbladder but all i i thought the carrier that these patients
00:23:01
have more colour but it is in a much more difficult
00:23:03
to to show benefited ditches and complications of obstruction there was
00:23:09
a significant difference interjected response rate in you know nine six
00:23:13
expose groups had about it and not like thirty percent rated shrinkage
00:23:17
and that said like topaz lined the midi interracial
00:23:20
responses significantly longer and and benefited a show greater
00:23:25
benefit over time in the habit in that you know it's it's it's a cumbersome out on him
00:23:30
an reinforcing also that these are durable immune responses and so
00:23:35
cannot have it the twenty formant rate responders header and around
00:23:38
the twenty percent eighty percent chance of remaining in response for
00:23:41
the number or um compared only six percent for the chemo i'm
00:23:45
so not nearly as face it by better candidate difference there
00:23:49
and safety was also quite reassuring and really no difference in
00:23:53
he high level safety parameters for convergence as versus the sega genesis
00:23:57
and the stereos they should rate for adverse events is less
00:24:00
than ten percent and the trainer so based on this data analysis
00:24:05
large face retrial the f. d. a. approved embolism out for
00:24:08
the to be added to chemotherapy when chances for your check answers
00:24:13
in october twenty twenty three minutes now and and alternate first line option so those are more subgroup in
00:24:21
coral analyses critical from talk has one things that these have not yet and propulsion keynote so from to
00:24:27
press one up by margaret data set entailed six
00:24:30
hundred and eighty fights and patience um and around and
00:24:36
three hundred each for placebo versus their development groups that
00:24:40
i'm really analyser key and sadness and and mutation profiling
00:24:45
and and we see the distribution of baseline mutations is what we'd expect remembrance day check
00:24:49
cancer patient and green are the ones that are potentially clinically actionable like id each one
00:24:54
and her two and then here we see the rated up to par to aberrations is
00:24:58
quite low in this group around three point four percent that was the baseline and if you
00:25:03
look at and outcomes according to the intention is to get an overall most scheme mutation
00:25:08
groups had pretty similar benefit according to while type versus alteration with the addition of divine or
00:25:15
well i was to highlight and that we're not so clear cut include fancy cancer a loss
00:25:21
and you know when a again is a corporate nasty factors but also of each year vacation
00:25:26
i was a little bit of difference would it have yes that the numbers are so slow leak
00:25:30
and they're hard to interpret and we don't have enough you should standardise for some of these
00:25:34
other groups like back i i've devoted euro but
00:25:37
overall similar benefit thing with response rate but on
00:25:41
just one exception ray and each one should a trend towards perhaps i'll a higher response rate
00:25:46
in the placebo arm then then train i'm really too small numbers to draw any conclusions but
00:25:54
i think i'm the the key point is that these analyses are really important any more data to be able
00:25:59
to refine which patients might benefit the most right now
00:26:03
the signal sees that most patients treated with target the purple
00:26:07
parsing higher again only exception where the yellow are as fire
00:26:10
purposely garments really at each one day again nine patients versus eighteen
00:26:14
inches super small numbers so to conclude a mutation of either anti
00:26:20
p. warmer campbell doesn't matter and take yeah one after value map
00:26:23
improve survival and first line advanced e. t. c. when combined
00:26:28
with genocide in class this that and the median overall survival implements
00:26:33
are modest by at the tele current there are greater proportion of
00:26:37
patients with prolonged response into survival in the invariance in both studies
00:26:42
and this benefit appears independent whether genders continued is minutes or not
00:26:48
an improvement seems pretty consistent across geographical molecular santa cruz the couple outliers that i
00:26:53
mentioned with like huge carry out that the numbers are too small the journey from conclusions
00:26:58
the and the time excel good suggests probably the greatest and it and it sure kind of project different you know
00:27:04
um unless differential benefactor got it but but this is highly contaminated by getting colour purity of the
00:27:10
cover and also sing some cases extra projects and groups that commissions quite
00:27:15
safe um and this they're collectively these data but a regulatory approvals in
00:27:20
the us purple commissions and already and and provide methods of other parts
00:27:24
that were literally you in japan and she questions in future directions on
00:27:31
we of course want to learn which patients benefit the most have a selector patience um and
00:27:36
we need to look at individuals mutations of larger sample sizes and i think this is where
00:27:40
we need to advocate as a as a feel for her and her canisters and it had
00:27:44
to try to let us to combined manhole other subgroup analyses i know that will be difficult
00:27:50
on the fundamental question for combinations like this is i we things energy it or some
00:27:54
other part so we just catching a few image when you're responders additive we are talking now
00:28:00
um we can tell i i think for sure yeah there is that our market data from the face to trial
00:28:05
um and the problem durations of responses i hope speak to the possibility of some some it's
00:28:10
synergy in at least some patients and then in terms of this is the new standard care
00:28:15
i would say yes i don't but not enough patients are getting uproar benefit that i'd want we need
00:28:19
to keep working to to make more progress that and
00:28:22
neither better combinations on identifying subgroups that benefit the most
00:28:28
and learning how to use these strategies in earlier stages of disease and patients
00:28:31
maybe how we're able to benefit more now to better in in in in response
00:28:36
so that i will thank you for your attention
00:28:45
range of roman schwinn shovel circulated for the movies so presentation with these different trials
00:28:51
uh_huh see that the visual track answers also getting caught hold no with possibilities
00:28:57
um do we have any questions or was that would like to uh i
00:29:05
uh okay let me just don't for a second or i can see them
00:29:14
yes furtively okay so uh i will read them to you how do you envision
00:29:22
the integration of chemotherapy minimal therapy in the first line treatment of we'll try
00:29:27
to answer him back seeing who was so whatever the progression free survival compared
00:29:32
to current standards of care which use um i i think it's you trials
00:29:39
don't doesn't it you know to show a small but significant improvement in overall survival
00:29:46
i'm andrew topaz p. f. s. as well so i think there
00:29:49
is a small improvement and a canister instead of patients get long benefit
00:29:53
and i like the case i showed you are there was a nice greater than six not chemo three interval
00:29:59
that was very valuable to that patient there's a second question
00:30:05
even the church in use nature really
00:30:08
correct answers include include addressing pneumonia little cancer
00:30:12
oh do you want to see pete vision selection criteria for comparing chemotherapy middle thirty regions
00:30:18
evolving to option myself because you won
00:30:21
in minimising potential adverse effects so i've seen
00:30:26
one clear conclusion propose that is is they're very minimal difference in safety by adding
00:30:31
the check when you know that are very only a very small tweaks percentage of
00:30:35
patients had any related toxicity announce that the c. d. was not as conservative state
00:30:41
we're using this is our standard for sign shut the combinations that we get all patients
00:30:46
in in chattanooga better unless they have a contra indications that just prior the for transplant
00:30:50
or we were um you have to take this or other other like out of the disease or whatever further won
00:30:59
could you elaborate on in the only going
00:31:02
or coming clinical trials investigating novel combinations of chemotherapy
00:31:07
an email therapy he shuns specific early in order for bill to a chance you're watching t.
00:31:14
v. and wants uh being assessed in these
00:31:16
trials and what preliminary results are image goes for
00:31:21
some different strategies to speaker immediately to um there are of course is the impulse i more drugs
00:31:28
uh add another i mean modifying age which again then we really have a hard time
00:31:33
sorting out what if the component contribution or only added to fit agent but i am brave
00:31:39
one five one trial is presented a g. i. s. code twenty twenty four last two months ago
00:31:44
one of the go looking at our to unseat gem for this and it has no that's
00:31:49
so i think that this is not to the true but at the beach opening other custom says
00:31:54
and it showed an improvement in progression free survival but not a significant improvement in
00:31:59
survival and then is is not moving forward going to that sort of backwards
00:32:04
clear cut strong advocacy and the challenges that probably not for drug regimen but there was the signal toward improvement
00:32:10
um and specifically in the price i like cell groups of patients that had two hours that look more like a g. c.
00:32:16
but by the transcript domino says showed greater benefit so that
00:32:19
that was what was presented it to ask other subgroup analyses
00:32:23
and so that's one approach to add more but that gets very extensive and
00:32:27
also very difficult to prove that you're actually achieving benefit without really large studies
00:32:32
and another strategy is to look at this question in some groups by molecular status and tried it
00:32:38
and harnessing units there be into the target there'd be and when i
00:32:42
do example the trial aren't rise it is looking at her to targeting
00:32:46
agents with chemotherapy plus minus i mean if there be in so i
00:32:51
think that's that the f. next with uh try as it the macy's
00:32:54
try getting around her to in some way with or without it you know there'd be no
00:33:02
no question also um we had some headache in switzerland with these differences the top was one
00:33:08
huge obvious non issue with the regulatory authorities
00:33:13
so um how do you do you interpret that this so uh less efficacy in this
00:33:20
trial in the non asian nations so that that wasn't who has um i think that's it
00:33:28
between the question of a lot of different prices including whether there's a difference in indigenous city or
00:33:33
underlying hepatitis b. exposure now that's the bigger falling
00:33:37
away from that belief in h. c. c. in particular
00:33:40
but it's more complicated than just virus that is there's a lot
00:33:43
of different practised patterns there's also differences in access to downstream clarity so
00:33:48
i personally think that those subgroups are are very difficult to interpret for
00:33:53
overall survival if you look at how has it look by response rate
00:33:58
but there is no difference i. e. elegy or location and i
00:34:01
think that's what i would just aren't the authorities with which is that
00:34:05
after a progression a lot is different according to region and underlined every disease
00:34:11
but until regression ideas you it cleaner read out of true efficacy obviously for
00:34:17
overall survival is at best overall i like that we're looking at sub groups
00:34:21
it's very hard to interpret trends without factoring in most regression and related
00:34:26
issues like access the density there to recover very so but response to
00:34:31
i think is how to interpret those forced us and he you know
00:34:35
nine six six showed alternate the greater benefits in but no i don't know
00:34:42
it's really nice together i think there's no clear cut difference well thank you thank you so much uh moving with
00:34:50
goes to the new york very busy leading in many
00:34:53
trials especially this last one controller congratulation cushion integrated with us
00:34:59
i'm going to also get up early may thank you very
00:35:02
much we much appreciated and we should good today and then
00:35:07
we will have oh you're not the breakfast we will have a coffee for her phone over so thank you very much
