Lung Cancer Clinical Trials: Advances in Immunotherapy


>>Welcome to the first ever Facebook Live
event for lung cancer awareness month. This event is a joint effort between the National
Cancer Institute or NCI and Lung Cancer Social Media also known as hashtag LCSM chat. We’ll be live on the NCI’s Facebook page for
30 minutes from 8 to 8:30 p.m. Eastern time. At the same time, LCSM chat is conducting
it’s regularly scheduled hour long tweet chat from 8 to 9 p.m. Eastern time. You can ask questions of myself or my guest
on the NCI’s Facebook page and we will do our best to answer those questions during
this discussion. Questions we don’t answer on air will be answered
in the comments soon afterwards. After the Facebook event ends, LCSM chat will
continue discussing tools and resources that help lung cancer patients access clinical
trials. More information about LCSM chat is available
at lcsmchat.com. We’re excited to one of the first groups of
the use the new Facebook Q and A feature using two different feeds. We’ve worked hard to make sure you have excellent
audio and video quality but please realize this is an experiment. I’m Janet Freeman Daily and I’m honored to
be moderating this discussion. I’m a blogger, science geek, lung cancer patient
activist, and co-founder of LCSM chat. Our topic today is immunotherapy for lung
cancer, new research and clinical trials. I’m honored to be working with Dr. Shakun
Malik, 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 talk
to 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 about
your background?>>Yes. So I have joined NCI about four years ago. Before that I worked as a clinician mainly
at the Lombardi Cancer Center at Georgetown. I led their thoracic oncology clinic where
we saw nearly diagnosed cancer patients and made a plan for their treatment. In between Georgetown and NCI, I also worked
at FDA where it was really an eye opening experience for me to learn how FDA looks at
approval of drugs and then at the NCI although my main work at this time is helping investigators
develop clinical trials in lung cancer, I continue to see patients in the clinical center
at NCI.>>It sounds like you’re well prepared for
your position.>>Thank you.>>So let’s define some terms. What is immunotherapy?>>So immunotherapy is a type of treatment
that 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 immunotherapies
are currently playing in lung cancer research and clinical trials?>>In lung cancer, the trend of approval for
chemo — for immunotherapies really started last year when FDA approved first immunotherapy
agent nivolumab for the second line patients with lung cancer. Now these are the patients who had already
had chemotherapy as a first line and then they — when they progressed, it showed — the
clinical trial showed that nivolumab compared to chemotherapy improved survival. Since then, there — the field has moved further
ahead 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 improvement
in overall survival and progression free survival in patients against chemotherapy. It’s a lot of exciting things happening in
the field of immunotherapy and lung cancer. And there are, obviously, a number of trials
that are also ongoing looking at maintenance or looking at combinations of chemo — immunotherapies
with 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 talked
about the Lung-MAP trial for squamous cell lung cancer. Can you explain what this trial and the role
that immunotherapy’s played in it?>>Lung-MAP is a first trial of lung cancer
as a personalized therapy that was developed as a master protocol with NCI and in collaboration
with pharma at FNIH [phonetic]. It was a first public private partnership
trial that started a couple of years ago. And what happened was at the time immunotherapies
were not approved for lung cancer. So we were doing clinical trials where we
were 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 immunotherapy
arm that was also experimental. So eventually, as you know, that immunotherapy
became approved was an approved therapy and improved survival in this second line lung
cancer patients. We actually had to modify the trial as we
did not think that chemotherapy was a good control anymore since that was not as good
as immunotherapy. So now we actually have patients who have
never had immunotherapy that they are tested against nivolumab that reaches a standard
of care in these patients against a combination of immunotherapy. We also have a single agent drugs that are
being tested for genetically abnormal tissue in those lung cancer patients. So immunotherapy arm has been added. We are also looking forward to another immunotherapy
arm that is going to be added in a combination in patients who are going to be refracted
to immunotherapy. So we had to modify this clinical trial as
the drugs became [inaudible] and we had more knowledge of what drugs and what immunotherapies
work in these patients.>>So, trying to simplify this a little because
there’s an awful lot of arms it sounds like now.>>Yes.>>So the Lung-MAP trial is for patients who
have squamous cell lung cancer and when they decide they want to enter the trial, what
happens?>>So if they want to decide to enter the
trial, if they’ve — their tissue will be tested for genetic abnormalities. If they have one of the genetic abnormality
for 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 nivolumab
with 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 have
not become refractory to that. So we have a combination of immunotherapy. So we’re going to have, at least, two different
trials amongst these arms in Lung-MAP where patients will be able to go on immunotherapy
but if they have genetic abnormality they can go into one of the arms that we have drug
for. Trying to have a lot of choices.>>So for squamous cell patients, this actually
simplifies things. They don’t have to look at all of the different
trials that might be out there. They can be within one trial but go to the
arm that seems to have the best chance of being appropriate for that.>>If they are eligible for, as you know there
could be other trials but this gives them an option that they — this trial can — they
may be eligible for one of the arms or an immunotherapy arm. And it gives them a broader choice of not
have 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 criteria
and if we have a drug for their genetic abnormality and if they will be eligible for immunotherapy,
they can go on immunotherapy.>>Okay. So these patients previously were — would
be one of these targeted therapies or they would be on chemo and now — many of them
have the option to go on immunotherapy. Let’s talk a little bit about the side effects
that patients experience for immunotherapy. How are those different than the side effects
they might see for chemo?>>So chemotherapy, you know works on all
growing cells. So that’s why we have a different kind of
toxicities 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 not
differentiate between normal cell and abnormal cell. Luckily chemotherapies killed the abnormal
cells so that’s how we treated lung or any kind of cancer. But immunotherapies although are less toxic
but let me just take a pause, but they also have toxicities. And these toxicities may are less intense
some 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 related
to 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.>>Okay. So in lung cancer, most of the immunotherapies
that we have available target individual proteins. The PD-L1 or PD 1 but there are other types
of immunotherapies that are coming down the pike. Can you talk a little bit about those? There’s vaccines.>>Yes.>>There’s –>>There are vaccines. There are combination therapies. So they are all in early development at this
time. And it is a combination of immunotherapies
that not only work on PD 1 or PD-L1, they work on CDLA-4 and other immune checkpoints
but they are early in the development. Right now what is approved for lung cancer
are PD 1 and PD-L1 drugs. And [inaudible].>>Okay. So there are others coming also which is great.>>There is others [inaudible].>>Okay. Another clinical trial we talked about last
year 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 ALCHEMIST
in the ALCHEMIST trial. So what ALCHEMIST is a trial for early stage
lung cancer patients. These are the patients who have stage 1 to
3a lung cancer that has been completely removed. And so then they will get standard of care
which is usually chemotherapy. And after that, patients still had a 50% chance
of 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 ALK
mutations, they would go on crizotinib for two years to test if additional targeted therapies
improved survival in these patients beyond what we get with chemotherapy. So when immunotherapies got approved, we again
had to modify this trial because now we know that immunotherapies in metastatic setting
also help patients with lung cancer. So there were two changes we had to consider
for ALCHEMIST that happened. One was that ALCHEMIST was only for patients
with non-squamous histology because as you know that EGFR and ALK mutations are in non-squamous
histology. On the other hand, immunotherapies don’t only
work with non-squamous, it also works in squamous cell histology. So we had to add another cohort of lung cancer
patients that had squamous histology as well. And we also have now a trial added which is
immunotherapy with nivolumab after they have had standard of care after surgery and versus
observation. So again, in this study we will test whether
addition of immunotherapy after chemotherapy will improve survival in these patients.>>Okay. Can you please explain the role of genetic
testing in screening and qualifying for these clinical trials? We’ve talked about identifying which drug
might match a particular patient’s lung cancer. So what sort of things are you talking about
screening for and how do they do that?>>It depends on the clinical trial. For example, it also will depend on what kind
of 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 that
we 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 trying
to block by a drug and if we see after a certain number of patients it doesn’t work, we can
close that arm. So it will really depend, at the time, when
a patient is newly diagnosed and then develops progression they can have their genetic testing
done even at that time. And at the time of progression can right away
go into the Lung-MAP trial if their genetic abnormality — for their genetic abnormality
we have an arm ongoing at that time. Similarly for ALCHEMIST, again for ALCHEMIST
we are only testing two genetic abnormalities which is ALK, ALK translocation and EGFR. And if they are negative for that, then they
will be tested for PD-L1 and they will go on PD-L1 nivolumab trial. Now for nivolumab trial, you don’t have to
be PD-L1 positive. This is for both PD-L1 positive and negative
since 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 positive
benefit more but we also have seen that they can benefit to some extent PD-L1 negative. So both types — so both PD-L1 positive as
well as negative can go on ALCHEMIST.>>Okay. 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 trial
would be — it will be paid by the NCI for screening.>>Okay. So we’ve been talking about clinical trial
options for patients that have particular targets. We’ve talked about immunotherapy. Are there any efforts looking into whether
or not patients who have EGFR, ALK, or ROS1 benefit from combining their targeted therapy
with an immunotherapy?>>There are some trials that are looking
at this at the moment but as you know, that is something that we need to start with a
smaller pilot trials. And if we do have a pre-clinical and clinical
benefit then it can go into large randomized trials. There is ALK plus immunotherapy trial ongoing
at the moment.>>We’ve been using the terms PD-1 and PD-L1
but we haven’t really defined what those are. Could you talk a little bit more about the
PD-1 blockade and what that’s about?>>So this is — these are the enzymes that
are proteins that are found in tumor tissue. And so these — if they are the ones if you
block them, then the cancer cells die. So that’s why they are called PD-L1 and PDL. And so these are expressions of the protein
in the tumor cells. And patients can be positive or negative –>>Okay.>>– in their tissue. So you can — we can test this on the tumor
tissue.>>So the PD-1 as I understand it is a protein
that’s on the white cell.>>Yes. 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.>>Yes. But not necessarily correct.>>Okay. Okay. So there are other types of immunotherapies
also. One of the things that a question that’s come
in is about adoptive transfer of T-cells. Could you talk a little bit about what that
is?>>Right. So you can have adoption of the T-cells where
you can transfer the immunotherapy — immune cells and that can block. Blocking them can help cancer cells. So those are all the things that are being
tested at this time but we don’t have drugs that have either approved or have been tested
in the big clinical trials at this time.>>There are some clinical trials that are
looking at it though.>>Right.>>Right. Okay. All right. Let’s see another question. So are there other types of immunotherapies
that I’m getting a question. Like cancer vaccines. Can you talk a little bit about how those
work?>>So again cancer vaccines are that you try
to make — you give the vaccines and again, make your own immune system fight cancer. So there have been this — vaccines have been
tested many, many years ago and so far, there has not been a positive clinical trial that
has led to an FDA approval of these vaccines for lung cancer. But that doesn’t mean that won’t happen in
future. It doesn’t mean that we are not going to be
able to refine these vaccines and be able to help in future but we’ll see how the field
goes.>>Okay. Some patients with other cancers like melanoma
have had long-term response to immunotherapies. Are we seeing that in lung cancer also?>>This is — yes. So this is an interesting question that we
are looking at. So what happens is that most of these patients
may not — even though they benefit and have overall survival but when you look at the
survival curves, you’re going to always have a tail end which means that at the end of
the 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 being
done and who are these patients. I mean, as you and I talk, that these patients
could be who have PD-L1 expression but that’s not the whole story because we know that it
works better in this. But there is something about those patients
that where PD-L1 or not only PD-L1 there maybe something in their system or body. Why these patients live longer than most of
the patients what we call, you know, we have a clinical trial that we’re looking at these
patients called exceptional responders. Why do they exceptionally do well. So that is a lot of interest brought by NCI
and other investigators to look at those patients. Look at their genomics [phonetic]. Look at their, you know, tumor tissue to see
why are these patients responding and why are they doing better than other patients. And that you see a lot in immunotherapy.>>Okay.>>You see a lot in other targeted therapies
as well but immunotherapy it’s much more pronounced that you see that big tail end.>>Okay. So we’ve talked a bit about clinical trials. Are these clinical trials we’re talking about
only for patients with advanced cancer and if a patient is interested in a clinical trial
how do they find them if their doctor is not able to help them find it?>>So clinical trials are not only for advanced
patients as we just talked. ALCHEMIST is for patients who have early stage
lung cancer. And Lung-MAP, on the other hand, is for patients
who have advanced staged lung cancer. There are some trials that are ongoing and
even earlier stage where we are testing whether immunotherapy in new [inaudible] which means
even before they have had surgery. Whether that makes a difference in this space
against studies are just being started and it will take us few more years to have an
answer to that. So it can be for any early stage or late stage
patients, we also are going to be having a trial started for maintenance that patient
has advanced stage then they respond to chemotherapy or immunotherapy and how long we can treat
them 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 these
clinical trials? So one of the ways we are at NCI looking at
making 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 cancer
help line and their physician as well can help them find the clinical trials.>>And we will be also discussing more resources
and 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 resource
as well.>>Yes. So we just have a little bit of time. I want to ask quickly. How can people access clinical trials if they
don’t live near a major academic cancer center?>>Janet, you’ll be surprised to know that
60% 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 to
say, you know, if patient lives very far from academic center that they — you know how
far that that community based center will be but it will be much easier for them to
find if they can go on the trials.cancer.gov or talk to their physician and find out where
can they get on these clinical trials. And again, I’m very happy to say that more
than 60% of our sites are in community based centers.>>Okay. We have another question that came in from
the audience. Can patients on immunotherapies initially
see their cancer progress or might patients on immunotherapies take a longer time to see
a response than possibly on other treatments?>>That’s a very good question. An excellent question actually. Yes. We are seeing that much less happen with these
immunotherapies but it can happen. So it takes — when an immunotherapy is given
or these drugs given, sometimes in the beginning we didn’t know about this phenomena called
pseudoprogression, the patient’s tumor may show that it is bigger but it is usually what
we have noted is that it is from all these immune cells coming around the tumor and trying
to, 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 same
size and you know, we may be concerned oh it’s not shrinking but then you see that these
patients will live a long time with just the same size in the tumor. So the doctors know this phenomena and again
it was much more seen pronounced with another type of immunotherapies called CLTA-4 cells
but we do see sometimes with these immunotherapies also and then we just follow these patients
and do another scan in a few weeks and feel better when these tumors start shrinking and
they start — cancer patients continue to do well.>>Okay. Well we’re approaching the end of our Facebook
Live time. So when this event ends, please join us in
the ongoing Lung Cancer Social Media chat which we’ll be discussing tools and resources
to help patients access lung cancer clinical trials. To participate, just search Twitter for the
hashtag LCSM and include the hashtag LCSM in all your tweets. If we have any questions that were posted
that we didn’t get to, answers will continue to be posted in the comments section on the
NCI’s Facebook page. You can see a recording of this video soon
on 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 in
closing Dr. Malik, Shakun?>>Thank you, Janet. And I thank you for giving an opportunity
to talk with you today. And it –>>Well, I appreciate your — go ahead.>>Thank you. And if you have any questions or patients
have any questions please feel free to send us questions and I’ll be more than happy to
respond 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 information
with patients. So we are closing out this Facebook Live even
for lung cancer awareness month. This is Janet Freeman Daily and –>>This is Shakun Malik from NCI. Thank you.>>Okay. Signing off.>>Thank you.>>Thank you.