>> welcome to the first ever facebook liveevent for lung cancer awareness month. this event is a joint effort between the nationalcancer institute or nci and lung cancer social media also known as hashtag lcsm chat. we'll be live on the nci's facebook page for30 minutes from 8 to 8:30 p.m. eastern time. at the same time, lcsm chat is conductingit's regularly scheduled hour long tweet chat from 8 to 9 p.m. eastern time. you can ask questions of myself or my gueston the nci's facebook page and we will do our best to answer those questions duringthis discussion. questions we don't answer on air will be answeredin the comments soon afterwards.
after the facebook event ends, lcsm chat willcontinue discussing tools and resources that help lung cancer patients access clinicaltrials. more information about lcsm chat is availableat lcsmchat.com. we're excited to one of the first groups ofthe use the new facebook q and a feature using two different feeds. we've worked hard to make sure you have excellentaudio and video quality but please realize this is an experiment. i'm janet freeman daily and i'm honored tobe moderating this discussion. i'm a blogger, science geek, lung cancer patientactivist, and co-founder of lcsm chat.
our topic today is immunotherapy for lungcancer, new research and clinical trials. i'm honored to be working with dr. shakunmalik, head of thoracic oncology therapeutics at the national cancer institute. welcome dr. malik. >> thank you janet and good evening. and i am honored to be here with you to talkto you and my patients about the lung cancer immunotherapy. and please call me shakun. >> oh thank you very much, shakun.
so would you please tell us a little bit aboutyour background? >> yes. so i have joined nci about four years ago. before that i worked as a clinician mainlyat the lombardi cancer center at georgetown. i led their thoracic oncology clinic wherewe saw nearly diagnosed cancer patients and made a plan for their treatment. in between georgetown and nci, i also workedat fda where it was really an eye opening experience for me to learn how fda looks atapproval of drugs and then at the nci although my main work at this time is helping investigatorsdevelop clinical trials in lung cancer, i
continue to see patients in the clinical centerat nci. >> it sounds like you're well prepared foryour position. >> thank you. >> so let's define some terms. what is immunotherapy? >> so immunotherapy is a type of treatmentthat works with your own immune system to help fight cancer cells. so instead of attacking the cancer cells directly,the drugs help your own immune system to fight cancer that it is normally supposed to do.
>> okay. and can you please explain the role that immunotherapiesare currently playing in lung cancer research and clinical trials? >> in lung cancer, the trend of approval forchemo -- for immunotherapies really started last year when fda approved first immunotherapyagent nivolumab for the second line patients with lung cancer. now these are the patients who had alreadyhad chemotherapy as a first line and then they -- when they progressed, it showed -- theclinical trial showed that nivolumab compared to chemotherapy improved survival.
since then, there -- the field has moved furtherahead and we now have actually three more drugs that are approved. and recently we had first drug approved, pambrol[phonetic], for patients in first line. this immunotherapy actually showed improvementin overall survival and progression free survival in patients against chemotherapy. it's a lot of exciting things happening inthe field of immunotherapy and lung cancer. and there are, obviously, a number of trialsthat are also ongoing looking at maintenance or looking at combinations of chemo -- immunotherapieswith chemotherapies or with other chemotherapies and immunotherapies in this field.
>> and we have several approved drugs also. okay. so last year in our google hangout, we talkedabout the lung-map trial for squamous cell lung cancer. can you explain what this trial and the rolethat immunotherapy's played in it? >> lung-map is a first trial of lung canceras a personalized therapy that was developed as a master protocol with nci and in collaborationwith pharma at fnih [phonetic]. it was a first public private partnershiptrial that started a couple of years ago. and what happened was at the time immunotherapieswere not approved for lung cancer.
so we were doing clinical trials where wewere testing patient's tissue and if they had a genetic abnormality in their tissue,they would go into one of the arms and we also were testing it against chemotherapy. we did have, at that time, an immunotherapyarm that was also experimental. so eventually, as you know, that immunotherapybecame approved was an approved therapy and improved survival in this second line lungcancer patients. we actually had to modify the trial as wedid not think that chemotherapy was a good control anymore since that was not as goodas immunotherapy. so now we actually have patients who havenever had immunotherapy that they are tested
against nivolumab that reaches a standardof care in these patients against a combination of immunotherapy. we also have a single agent drugs that arebeing tested for genetically abnormal tissue in those lung cancer patients. so immunotherapy arm has been added. we are also looking forward to another immunotherapyarm that is going to be added in a combination in patients who are going to be refractedto immunotherapy. so we had to modify this clinical trial asthe drugs became [inaudible] and we had more knowledge of what drugs and what immunotherapieswork in these patients.
>> so, trying to simplify this a little becausethere's an awful lot of arms it sounds like now. >> so the lung-map trial is for patients whohave squamous cell lung cancer and when they decide they want to enter the trial, whathappens? >> so if they want to decide to enter thetrial, if they've -- their tissue will be tested for genetic abnormalities. if they have one of the genetic abnormalityfor which we have a drug that we are testing, they will go into that arm. if they do not, they -- if they have had immunotherapy,we have a clinical trial for them which is
nivolumab versus the combination of nivolumabwith another immunotherapy. now we are going to be, in very near future,opening another trial which is for the patients who have also had immunotherapy and they havenot become refractory to that. so we have a combination of immunotherapy. so we're going to have, at least, two differenttrials amongst these arms in lung-map where patients will be able to go on immunotherapybut if they have genetic abnormality they can go into one of the arms that we have drugfor. trying to have a lot of choices. >> so for squamous cell patients, this actuallysimplifies things.
they don't have to look at all of the differenttrials that might be out there. they can be within one trial but go to thearm that seems to have the best chance of being appropriate for that. >> if they are eligible for, as you know therecould be other trials but this gives them an option that they -- this trial can -- theymay be eligible for one of the arms or an immunotherapy arm. and it gives them a broader choice of nothave to go from, you know, one trial to the other and maybe be able to -- be eligible,of course, you know, one has to see whether these patients meet all the eligibility criteriaand if we have a drug for their genetic abnormality
and if they will be eligible for immunotherapy,they can go on immunotherapy. so these patients previously were -- wouldbe one of these targeted therapies or they would be on chemo and now -- many of themhave the option to go on immunotherapy. let's talk a little bit about the side effectsthat patients experience for immunotherapy. how are those different than the side effectsthey might see for chemo? >> so chemotherapy, you know works on allgrowing cells. so that's why we have a different kind oftoxicities with chemotherapies where you know, the blood cells will drop in numbers. patients get -- got infections and sepsis.
and the -- so that -- you know it did notdifferentiate between normal cell and abnormal cell. luckily chemotherapies killed the abnormalcells so that's how we treated lung or any kind of cancer. but immunotherapies although are less toxicbut let me just take a pause, but they also have toxicities. and these toxicities may are less intensesome of the chemotherapy toxicities but they can also be annoying or they can intense. >> very intense.
>> or they can be -- you know, serious. so the more common toxicities are relatedto immune like you know, patients may have any liver toxicities. they can have lung toxicities but in general,these are thought to be different and milder than chemotherapy. so in lung cancer, most of the immunotherapiesthat we have available target individual proteins. the pd-l1 or pd 1 but there are other typesof immunotherapies that are coming down the pike. can you talk a little bit about those?
there's vaccines. >> there's -- >> there are vaccines. there are combination therapies. so they are all in early development at thistime. and it is a combination of immunotherapiesthat not only work on pd 1 or pd-l1, they work on cdla-4 and other immune checkpointsbut they are early in the development. right now what is approved for lung cancerare pd 1 and pd-l1 drugs. and [inaudible].
so there are others coming also which is great. >> there is others [inaudible]. another clinical trial we talked about lastyear was the alchemist clinical trial. is there anything new there? >> so similar changes we had to make for lung-map. we had to also make modifications of alchemistin the alchemist trial. so what alchemist is a trial for early stagelung cancer patients. these are the patients who have stage 1 to3a lung cancer that has been completely removed. and so then they will get standard of carewhich is usually chemotherapy.
and after that, patients still had a 50% chanceof relapse. so what alchemist was doing was testing patients'tissue and if they had egfr, they would go on erlotinib for two years and if they alkmutations, they would go on crizotinib for two years to test if additional targeted therapiesimproved survival in these patients beyond what we get with chemotherapy. so when immunotherapies got approved, we againhad to modify this trial because now we know that immunotherapies in metastatic settingalso help patients with lung cancer. so there were two changes we had to considerfor alchemist that happened. one was that alchemist was only for patientswith non-squamous histology because as you
know that egfr and alk mutations are in non-squamoushistology. on the other hand, immunotherapies don't onlywork with non-squamous, it also works in squamous cell histology. so we had to add another cohort of lung cancerpatients that had squamous histology as well. and we also have now a trial added which isimmunotherapy with nivolumab after they have had standard of care after surgery and versusobservation. so again, in this study we will test whetheraddition of immunotherapy after chemotherapy will improve survival in these patients. can you please explain the role of genetictesting in screening and qualifying for these
clinical trials? we've talked about identifying which drugmight match a particular patient's lung cancer. so what sort of things are you talking aboutscreening for and how do they do that? >> it depends on the clinical trial. for example, it also will depend on what kindof clinical trial or the drug in that arm is open. for example, i am talking about lung-map. so we have arms -- one of the things thatwe are able to do in these master protocols is depending on as we added immunotherapies,we can also subtract the drugs that don't
work. so if we have a target that we are tryingto block by a drug and if we see after a certain number of patients it doesn't work, we canclose that arm. so it will really depend, at the time, whena patient is newly diagnosed and then develops progression they can have their genetic testingdone even at that time. and at the time of progression can right awaygo into the lung-map trial if their genetic abnormality -- for their genetic abnormalitywe have an arm ongoing at that time. similarly for alchemist, again for alchemistwe are only testing two genetic abnormalities which is alk, alk translocation and egfr.
and if they are negative for that, then theywill be tested for pd-l1 and they will go on pd-l1 nivolumab trial. now for nivolumab trial, you don't have tobe pd-l1 positive. this is for both pd-l1 positive and negativesince we don't know at this time who are the best people who are benefited by this drug. we know that the people who are pd-l1 positivebenefit more but we also have seen that they can benefit to some extent pd-l1 negative. so both types -- so both pd-l1 positive aswell as negative can go on alchemist. so if people are interested in these trials,the trial pays for the testing if they meet
all the criteria? >> that's right. if they meet all the other criteria, the trialwould be -- it will be paid by the nci for screening. so we've been talking about clinical trialoptions for patients that have particular targets. we've talked about immunotherapy. are there any efforts looking into whetheror not patients who have egfr, alk, or ros1 benefit from combining their targeted therapywith an immunotherapy?
>> there are some trials that are lookingat this at the moment but as you know, that is something that we need to start with asmaller pilot trials. and if we do have a pre-clinical and clinicalbenefit then it can go into large randomized trials. there is alk plus immunotherapy trial ongoingat the moment. >> we've been using the terms pd-1 and pd-l1but we haven't really defined what those are. could you talk a little bit more about thepd-1 blockade and what that's about? >> so this is -- these are the enzymes thatare proteins that are found in tumor tissue. and so these -- if they are the ones if youblock them, then the cancer cells die.
so that's why they are called pd-l1 and pdl. and so these are expressions of the proteinin the tumor cells. and patients can be positive or negative -- >> -- in their tissue. so you can -- we can test this on the tumortissue. >> so the pd-1 as i understand it is a proteinthat's on the white cell. yes. that's correct. >> which is part of the immune system.
and pd-l1 is on the tumor cell. >> it can be on tumor cells yes. >> but not necessarily. but not necessarily correct. so there are other types of immunotherapiesalso. one of the things that a question that's comein is about adoptive transfer of t-cells. could you talk a little bit about what thatis? >> right. so you can have adoption of the t-cells whereyou can transfer the immunotherapy -- immune
cells and that can block. blocking them can help cancer cells. so those are all the things that are beingtested at this time but we don't have drugs that have either approved or have been testedin the big clinical trials at this time. >> there are some clinical trials that arelooking at it though. all right. let's see another question. so are there other types of immunotherapiesthat i'm getting a question. like cancer vaccines.
can you talk a little bit about how thosework? >> so again cancer vaccines are that you tryto make -- you give the vaccines and again, make your own immune system fight cancer. so there have been this -- vaccines have beentested many, many years ago and so far, there has not been a positive clinical trial thathas led to an fda approval of these vaccines for lung cancer. but that doesn't mean that won't happen infuture. it doesn't mean that we are not going to beable to refine these vaccines and be able to help in future but we'll see how the fieldgoes.
some patients with other cancers like melanomahave had long-term response to immunotherapies. are we seeing that in lung cancer also? >> this is -- yes. so this is an interesting question that weare looking at. so what happens is that most of these patientsmay not -- even though they benefit and have overall survival but when you look at thesurvival curves, you're going to always have a tail end which means that at the end ofthe curve there is going to be a number of patients that continue to live long. and so a lot of research at this time is beingdone and who are these patients.
i mean, as you and i talk, that these patientscould be who have pd-l1 expression but that's not the whole story because we know that itworks better in this. but there is something about those patientsthat where pd-l1 or not only pd-l1 there maybe something in their system or body. why these patients live longer than most ofthe patients what we call, you know, we have a clinical trial that we're looking at thesepatients called exceptional responders. why do they exceptionally do well. so that is a lot of interest brought by nciand other investigators to look at those patients. look at their genomics [phonetic].
look at their, you know, tumor tissue to seewhy are these patients responding and why are they doing better than other patients. and that you see a lot in immunotherapy. >> you see a lot in other targeted therapiesas well but immunotherapy it's much more pronounced that you see that big tail end. so we've talked a bit about clinical trials. are these clinical trials we're talking aboutonly for patients with advanced cancer and if a patient is interested in a clinical trialhow do they find them if their doctor is not able to help them find it?
>> so clinical trials are not only for advancedpatients as we just talked. alchemist is for patients who have early stagelung cancer. and lung-map, on the other hand, is for patientswho have advanced staged lung cancer. there are some trials that are ongoing andeven earlier stage where we are testing whether immunotherapy in new [inaudible] which meanseven before they have had surgery. whether that makes a difference in this spaceagainst studies are just being started and it will take us few more years to have ananswer to that. so it can be for any early stage or late stagepatients, we also are going to be having a trial started for maintenance that patienthas advanced stage then they respond to chemotherapy
or immunotherapy and how long we can treatthem with these drugs and maintain them. so it can be on any lung cancer patient. it is a matter of finding the right trial. now the question is how do patients find theseclinical trials? so one of the ways we are at nci looking atmaking the navigation for patients easier so that we can help them. they can try to check at trials.cancer.gov. that will help them or they can call our cancerhelp line and their physician as well can help them find the clinical trials.
>> and we will be also discussing more resourcesand ways to find clinical trials on the hashtag lcsm chat on twitter at the same time. >> yes, and -- >> so. >> so i thought -- >> go ahead. >> yeah so that you will give them that resourceas well. so we just have a little bit of time. i want to ask quickly.
how can people access clinical trials if theydon't live near a major academic cancer center? >> janet, you'll be surprised to know that60% of our sites for both lung-map and alchemist are in community based sites. so -- >> oh that's good to know. >> so -- you know it will be hard for me tosay, you know, if patient lives very far from academic center that they -- you know howfar that that community based center will be but it will be much easier for them tofind if they can go on the trials.cancer.gov or talk to their physician and find out wherecan they get on these clinical trials.
and again, i'm very happy to say that morethan 60% of our sites are in community based centers. we have another question that came in fromthe audience. can patients on immunotherapies initiallysee their cancer progress or might patients on immunotherapies take a longer time to seea response than possibly on other treatments? >> that's a very good question. an excellent question actually. we are seeing that much less happen with theseimmunotherapies but it can happen. so it takes -- when an immunotherapy is givenor these drugs given, sometimes in the beginning
we didn't know about this phenomena calledpseudoprogression, the patient's tumor may show that it is bigger but it is usually whatwe have noted is that it is from all these immune cells coming around the tumor and tryingto, you know, go around it and then eventually it will calm down and then it will start shrinking. and also sometimes these tumors may stay samesize and you know, we may be concerned oh it's not shrinking but then you see that thesepatients will live a long time with just the same size in the tumor. so the doctors know this phenomena and againit was much more seen pronounced with another type of immunotherapies called clta-4 cellsbut we do see sometimes with these immunotherapies
also and then we just follow these patientsand do another scan in a few weeks and feel better when these tumors start shrinking andthey start -- cancer patients continue to do well. well we're approaching the end of our facebooklive time. so when this event ends, please join us inthe ongoing lung cancer social media chat which we'll be discussing tools and resourcesto help patients access lung cancer clinical to participate, just search twitter for thehashtag lcsm and include the hashtag lcsm in all your tweets. if we have any questions that were postedthat we didn't get to, answers will continue
to be posted in the comments section on thenci's facebook page. you can see a recording of this video soonon the nci's website and youtube pages. so we have just a minute or two longer. do you have something you'd like to say inclosing dr. malik, shakun? >> thank you, janet. and i thank you for giving an opportunityto talk with you today. and it -- >> well, i appreciate your -- go ahead. and if you have any questions or patientshave any questions please feel free to send
us questions and i'll be more than happy torespond to those questions. >> all right. well thank you shakun for joining me. it's always a pleasure to talk with you. i appreciate your willingness to share informationwith patients. so we are closing out this facebook live evenfor lung cancer awareness month. this is janet freeman daily and -- >> this is shakun malik from nci. thank you.
signing off.
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