00:05
Byeong Yoon, PhD: Hello everyone. Today we’re here together to discuss a therapy for extensive-stage
small
cell lung cancer. It marks an exciting and important moment for these patients, their loved ones, their
caregivers, and the healthcare providers that treat them. A therapy that was FDA approved is
IMDELLTRA®,
also known as tarlatamab-dlle.1 We believe it represents a breakthrough treatment option for
patients with
extensive-stage small cell lung cancer.1,2 In addition, this approval represents Amgen’s
commitment to bring
meaningful innovation and hope to patients with hard-to-treat tumor types.1,2 Just a quick
housekeeping
note: the chat is available for you to submit any questions. In addition, in the chat you’ll find a link to
the full Prescribing Information for IMDELLTRA®. With that, we’re honored to have our esteemed
speaker and
renowned expert in lung cancer for this evening’s discussion, Dr David Waterhouse. Welcome, Dr Waterhouse.
Over to you.
01:11
Dr David Waterhouse, MD: Thank you for such a kind introduction. Appreciate it.
01:15
Byeong Yoon, PhD: The title of our presentation is Breakthrough Innovation: The First and Only
DLL3-Targeting Bispecific T-cell Engager, otherwise known as BiTE®, Therapy for Second-Line Plus
Extensive-Stage Small Cell Lung Cancer.1 Now in regards to the indication, IMDELLTRA®,
or
tarlatamab-dlle,
is indicated for the treatment of adult patients with extensive-stage small cell lung cancer with disease
progression on or after platinum-based chemotherapy.1 This indication is approved under an
accelerated
approval based on the overall response rate and duration of response observed in the trial.1
Continued
approval for this indication may be contingent upon verification and description of clinical benefit in a
confirmatory trial.1 There are some important safety information that I would like to review with
you.
Cytokine release syndrome or otherwise known as CRS, and neurological toxicity, including immune effector
cell–associated neurotoxicity syndrome is safety information that is relevant for this therapy.1
CRS,
including serious or life-threatening reactions, can occur in patients with
IMDELLTRA®.1
Initiating
treatment with IMDELLTRA® using the stepwise dosing schedule to reduce the incidence and severity
of CRS
should be followed.1
02:38
Byeong Yoon, PhD: IMDELLTRA® should be withheld until CRS resolves or permanently
discontinued based
on its
severity.1 Regarding neurotoxicity, it includes immune effector cell–associated neurotoxicity
syndrome,
otherwise known as ICANS, including serious or life-threatening reactions, can occur in patients receiving
IMDELLTRA®.1 Monitor patients for signs and symptoms of neurological toxicities,
including ICANS,
during
treatment, and treat promptly.1 Withhold IMDELLTRA® until ICANS resolves, or
permanently
discontinue based
on severity.1 This slide represents the table of contents for today’s presentation. Dr Waterhouse
will first
cover the background on IMDELLTRA®. He will then review the clinical results and then also
discuss the
management of the different safety aspects of this therapy, including CRS, ICANS, cytopenia, infections,
hepatotoxicity, and other adverse reactions. Next, he’ll review the IMDELLTRA® dosing and
administration.
And then lastly, the last two sections, he’ll discuss the patient counseling information and the resources
available, along with reviewing the important safety information again. With that, I hand it over to Dr
Waterhouse. Over to you.
04:02
Dr David Waterhouse, MD: Thank you very much and I’m really excited to be doing this promotional
program
tonight. This is my disclosure. The promotional product program is being presented on behalf of Amgen, the
program sponsor. It’s been reviewed and consistent with Amgen’s internal review policies and I have been
compensated for my time. About IMDELLTRA®… well you can’t talk about a product without talking
about the
disease we’re treating, and I think all of us who are viewing this program are aware of just how bad small
cell lung cancer can be. We know that this is a disease that can progress quickly,3 and you’d
better have a
plan for what you’re going to do with these patients. Two-thirds of the patients with small cell lung cancer
are going to present with extensive disease,4 and the five-year survival rate is only
7%,5 and more than 75%
of the time patients with this disease are going to experience disease progression.3 So, you’d
better be
ready to treat these patients. You’re going to have to have your first-line strategy and your strategy
beyond first line ready.
05:09
Dr David Waterhouse, MD: So IMDELLTRA®, you heard this indication read earlier, that it’s
indicated
for the
treatment with adult patients with extensive-stage small cell with disease progression on or after a
platinum-based chemotherapy.1 And as a result of the results we’re going to talk about a bit
later, you’re
going to see that this was approved by the FDA, under their Accelerated Approval Program.1
05:32
Dr David Waterhouse, MD: In terms of mechanism of action, this is the first and only DLL3-targeting
BiTE®
therapy that activates the patient’s own T cells to attack the DLL3-expressing cells.1 Now, we’ve
all heard
about BiTE® cells, and I think that the way to understand it is that you have a bispecific
antibody.6,7 One
part of the molecule is going to bind to the tumor antigen, so ~ 85 to 96% of patients with small cell
express DLL3.6,7 Because such a high number of patients express DLL3, we don’t have to be
required to do any
kind of biomarker testing.1,6,7
06:11
Dr David Waterhouse, MD: That’s an important point to understand. You do not have to do biomarker
testing.1
Because there’s so many of those, now you can target that with one side of the antibody while the other side
is binding to the T cell itself.1 Now you’re bringing the T cell in proximity to the tumor cell,
and you’re
going to activate that T cell for releasing inflammatory cytokines, and you get lysis of those
DLL3-expressing cells while again promoting further production of these T cells.1 So again,
classic BiTE®
cell technology.
06:49
Dr David Waterhouse, MD: Peppered inside of all of these kinds of talks are safety and warning
signals.
Truthfully, when I was younger, I only wanted to hear about the efficacy. But as I’ve gotten older and I’m
now treating so many of these patients, I realized that in order to be really good at what we do, we have to
understand the management of the side effects because that’s the difference between the good doctor and the
great doctor.
07:16
Dr David Waterhouse, MD: And, of course, the one that all of you want to hear about is cytokine
release
syndrome. IMDELLTRA® can cause CRS.1 It can be serious and
life-threatening,1 although
we’re going to see
the data as to what percentage of patients actually experienced that. It occurred in 55% of the patients,
including 34% of them that had Grade 1, 19% Grade 2, only 1.1% Grade 3, and 0.5% had Grade 4.1
Recurrent CRS
occurred in 24% of the patients and most of that was low-grade toxicity, 18% Grade 1 and 6% Grade
2.1 This
occurs early.1 43% of the patients occurred after their first dose, with 29% experiencing any
Grade CRS
after the second dose, and then only 9% of the patients experiencing CRS following the third dose or
later.1
08:13
Dr David Waterhouse, MD: If you look at it on what day of the infusion, following day 1, day 8, day
15,
those
percentages are 16%, 4.3, or 2.1% and we’ll see this presented graphically later in the
presentation.1
Importantly, the median time to the onset of all grade CRS from the most recent dose of
IMDELLTRA® was 13.5
hours.1 Although you can see the range is rather broad, 1 to 268 hours.1 The median
time to onset of ≥ Grade 2
CRS from the most recent dose was 14.6 hours.1 And again, you similarly see that very
wide range.1 And you need
to be able to recognize CRS, and so some of the symptoms that we tend to associate with this syndrome:
hypotension, fever, fatigue, tachycardia, headache, hypoxia, nausea, vomiting.1 And potentially
life-threatening
complications can include cardiac dysfunction, ARDS, or acute respiratory distress syndrome, neurologic
toxicity, renal and/or hepatic failure, and DIC [disseminated intravascular coagulation].1
09:29
Dr David Waterhouse, MD: So, we’re going to administer this drug IMDELLTRA® following a
recommended
stepped-up dosing,1 and we’ll administer concomitant medications after Cycle 1,1 and
this will be described
in Table 3. The important part is there’s an algorithm for managing this, and it is something that you can
follow.
09:49
Dr David Waterhouse, MD: Let’s now take a quick look at the clinical results. So
IMDELLTRA® was
studied in
the DeLLphi-301, phase 2, open-labeled, multicenter, multi-cohort clinical trial.1,7 In third
line or more
extensive-stage small cell, 99 patients were enrolled in this clinical trial.1 These are patients
with
extensive disease who had progression after receiving a previous treatment with a platinum-based
chemotherapy and at least one other line of therapy.1 IMDELLTRA® was then dosed 1
milligram on
day 1,
stepping it up to 10 milligrams then on
days 8, 15, and every two weeks thereafter.1 Treatment was then continued until disease
progression or
unacceptable toxicity.1
10:34
Dr David Waterhouse, MD: Fairly straightforward design. Primary outcome: overall response
rate.7
Select
secondary outcomes included duration of response, progression-free survival, overall survival, and AEs
during the treatment period.7 And here are some of the results. Remember this was after the
patients had
failed a platinum-based chemo and one other line, so heavily pretreated patients.1 You understand
those
patients have a poor prognosis.4 On the left-hand side of the slide, you can see the demographics
of the
patient population. The median age was 64, with 48% of the patients being over the age of 65 and 10% over
the age of 75.1 It was predominantly male, 72%.1 You can see the distribution by race,
ECOG status.1 Of
course, the majority were metastatic at the time of baseline.1 22% of the patients had brain
mets, and of
course as due to the inclusion criteria, you can see the prior therapies.1 Not surprisingly, most
of the
patients were former or current smokers.1
11:44
Dr David Waterhouse, MD: 74% had received a prior anti-PDL1 therapy and, again, highlighting 22% of
these
patients had brain mets.1 So, to continue talking about the efficacy, IMDELLTRA®
showed durable
efficacy in
patients with extensive-stage small cell.1 The primary endpoint of the study was objective
response rate,7
and you can see the objective response rate was 40%.1 Of those 40%, 2% of those patients were
complete
responders, while 38% were partial responses.1 And the confidence intervals for all of these
numbers can be
seen below. The median time to objective response was 1.4 months.7 The median follow-up for all
these
patients was 10.6 months.7
12:31
Dr David Waterhouse, MD: Among those who responded to IMDELLTRA®, the majority of the
patients responded for
more than 6 months, and 40% still responding at 1 year.1 You treat patients with small cell lung
cancer.
When you’re in the third line, are those the results you expect? The median duration of response, 9.7
months.1 68% of them responding more than 6 months and even 40% greater than or equal to 12
months.1
13:03
Dr David Waterhouse, MD: The safety and tolerability was evaluated in 187 patients with
extensive-stage
small cell, and adverse reactions occurred in greater than or equal to 15% of the patients.1 So,
on the
left-hand side of the slide, you can see some of the adverse reactions simply listed and then followed by
the Grade, any Grade followed by Grade 3 and Grade 4. And we’ll look at some of those specifically. On the
right-hand side, we’ve talked about some of the more standout features. The most common adverse reactions
occurring in greater than 20% of the patients were cytokine release syndrome, fatigue, pyrexia, dysgeusia,
decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.1
13:52
Dr David Waterhouse, MD: The permanent discontinuation rate, though due to these adverse events
occurred in
7% of the patients, and then dose interruptions occurred due to adverse reactions occurred in 27% of the
patients.1 And these adverse reactions that required dose interruptions in greater than or equal
to 2% of
the patients included fatigue, CRS, and respiratory tract infection.1 Now let’s go back over to
that
left-hand side and we can see the percent of patients who had toxicity, but we can also break it down by any
Grade and Grade 3, Grade 4, the most common toxicity was cytokine release syndrome, CRS, and that occurred
in 55% of our patients or a majority of our patients, Grade 3 or Grade 4 CRS, 1.6%.1 Fatigue, a
common
complaint among patients with extensive small cell, was heard in 51% of the patients with 10% of those
patients being Grade 3 or Grade 4, and we can keep going down looking at these percentages.1,3
15:01
Dr David Waterhouse, MD: Most of the Grade 3, Grade 4 toxicity with single digit toxicity, and any
Grade
toxicity you can see listed on the left-hand side there. These are all talking points and opportunities to
engage with the patient and their caregivers prior to administration so that they know what to expect. Now,
most CRS events were Grade 1 occurred following the first two doses of IMDELLTRA®.1
So, you can
see these
across the different doses on the bar graph below 34%, 19%, 1.1% and 0.5% of the patients experienced Grade
1, 2, 3, or 4 CRS, respectively.1 Recurrent CRS occurred in 24% of the patients, including 18%
that were
Grade 1 and 6% that were Grade 2.1 Looking at the left-hand slide, looking at the bar graph, you
see that
the toxicities occurred early on with the majority being on that first dose and again on the second dose and
much more infrequent as we go further down the course of treatment.7
16:12
Dr David Waterhouse, MD: The onset and duration of CRS with IMDELLTRA® is important and
has to be taken into
consideration when you’re treating these patients. The median onset of all grade CRS from the most recent
dose of IMDELLTRA® was 13.5 hours1 and the median duration, 4 days.7 Now
you can see
again a fairly wide
range as to when it might occur 1 to 268 hours and the median duration a little bit tighter, 2 to 6
days.1,7
The median time and onset of greater than or equal to 2 CRS from the most recent dose was 14.6
hours.1 So as
we’re educating our patients about when they might expect this to occur, we have to take these kind of
numbers into careful consideration. And same thing with the caregivers for those patients. Neurologic
toxicity, including ICANS, occurred in 47% of the patients with extensive small cell treated with
IMDELLTRA®.1 Looking at the right-hand side of this slide in the DeLLphi-300 and
DeLLphi-301
pooled safety
population, neurologic toxicity, including ICANS, occurred in 47% who received IMDELLTRA® and
this included
10% in Grade 3.1
17:30
Dr David Waterhouse, MD: Now, ICANS occurred in 9% of the patients treated, and if they were
retreated
recurrent ICANS occurred in 1.6% of the patient population.1 Now I think if you look at the
left-hand side,
we see this graphically that the ICANS and associated neurologic events across treatment doses shows a wider
distribution of occurrences and is not skewed towards that first or second dose as we saw in the
CRS.7 The
onset and time to resolution for ICANS with IMDELLTRA®, 29.5 days.1 So again, this is
going to
occur later
in the patient treatment schedule.1 The median onset from the first dose, you could see again a
wide range,
1 to 154 days, and this one takes a little longer to resolve, 33 days with a range going from 1 to 93
days.1
So it can occur several weeks after that IMDELLTRA® administration.1 So we talked
about those two
large
categories of side effects.
18:34
Dr David Waterhouse, MD: It’s not fair to talk to you about what can happen without telling you how
you can
and will manage these patients. So let’s talk about the management of CRS, ICANS, and some of the other side
effects that we’re more accustomed: to cytopenias, infections, and other adverse reactions.
IMDELLTRA® can
cause CRS (cytokine release syndrome), including serious or life-threatening toxicities.1 The
clinical signs
and symptoms of CRS include pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and
vomiting.1 Again, a teaching moment for both the patient and their caregivers. It’s an acute
systemic
inflammatory response and it’s characterized by these symptoms including fever and multi-organ
dysfunction.8
These symptoms can be progressive and usually present with fever at the onset.9 They can be
life-threatening, so you definitely want to be able to identify these patients, and some of the
life-threatening toxicities could include cardiac dysfunction, ARDS or acute respiratory distress syndrome,
neurologic toxicity, renal and/or hepatic failure, and DIC.1
19:52
Dr David Waterhouse, MD: Now CRS can be graded and was graded in the study using the 2019 American
Society
for Transplantation and Cellular Therapy consensus grading criteria.1 So here’s what CRS grading
looks like.
You are familiar with grading toxicities using common toxicity criteria and the like very similarly, Grade
1, Grade 2, Grade 3, Grade 4, and you can see it broken down by this.1 This is not something
you’re going to
try and memorize, although if you do enough of this after not too long, you actually will have this
memorized, but you want to know where you can access this information. Snip it, cut it, paste it in your
chart of the patient, especially if you’re not familiar with it, but you want to have access to the grading
and the management. So if you see this kind of toxicity, there are algorithms and strategies for managing
this. So you monitor the patient for this and then you can withhold or permanently discontinue based on
severity.1
20:59
Dr David Waterhouse, MD: So once again, don’t try to memorize this. None of us are that smart. What
we can
do is say we’re going to put this in a place where we can access it. You can access it online very easily.
As I said in my own practice, I will cut and snip something like this right into my patient’s chart because
it’s not just about me being reassured. I want my entire team to be reassured that they can handle this. So
Grade 1 toxicity you’re going to withhold until the event resolves.1 You might give systemic
treatment, but
that systemic treatment may be as simple as a Tylenol, and you can see the recommendations down the right
hand side of this slide and the interventions that will progressively become more invasive as the toxicity
increases all the way up to by the time you’re at Grade 4, you’re not going to be given this drug any
longer.1 You might even be managing this patient in an ICU and you could be considering
tocilizumab and
other interventions.1 Again, this will be available to you.
22:04
Dr David Waterhouse, MD: ICANS is a disorder that may occur in the CNS following treatment with
T-cell
engaging therapies like IMDELLTRA®,1,9 these neurologic toxicities can be graded and
you can see here the
grading system, Grade 1, Grade 2, Grade 3, Grade 4.1 They include something called an ICE
score1
and we’re
going to see what that ICE score is and how we calculate that in another slide coming forward. The point
being you’ll now assess for toxicity and grade the toxicity.1 The importance of the grading is
that your
management strategy then will be dependent upon the grade of the toxicity.1
22:47
Dr David Waterhouse, MD: The ICE scoring tool is recommended as an encephalopathy assessment tool in
the
grading of ICANS following treatment within IMDELLTRA®, and you can see the tool
itself.1,9 We’re
going to
look at orientation, year, month, city, hospital, score points. We’re going to name 3 objects.9
Again, give
this a score.9 Can they follow commands? And you see some examples presented. Can you write? We
actually use
that exact sentence, “our national bird is the bald eagle,” and can you count backwards? We then assign the
number of points to this and that gives you the ICE score, which plays into the grading score that we saw
earlier.9 And all of this plays into our management strategy for the patient when they experience
this
toxicity, if it should occur.9
23:41
Dr David Waterhouse, MD: Earlier we talked about grading toxicity, and we’re monitoring patients for
neurologic toxicity in ICANS, and we will withhold or permanently discontinue IMDELLTRA® based on
severity.1
So once we have graded these patients, there are management strategies.1 So Grade 1, Grade 2,
Grade 3, Grade
4, and you can see to the right hand side of the slide what those management strategies may look like.
24:11
Dr David Waterhouse, MD: Now, some of the side effects that we are used to with our patients with
small
cell lung cancer…10 Cytopenias, they weren’t as common as what we see with many of our
drugs,1,10 but again,
I think most of us are feeling pretty comfortable managing cytopenias. Infections can occur, largely as a
result of those cytopenias, and you can see the management and dose modifications that are coming along with
the label based on the management that was done inside the clinical trial.1,10 Hepatotoxicity,
other adverse
events, Grade 3, Grade 4, these are very similar to what you’ve grown accustomed to with treating patients
with other chemotherapies for small cell.10,11
24:55
Dr David Waterhouse, MD: So we talked about the grading of toxicity. We talked about management
strategies
based upon the grade of the toxicity. Now let’s talk a little bit about recommendations for restarting
IMDELLTRA® therapy after there’s been a dosage delay, and you can see the strategy outlined in
this chart
below. Again, this is not something you’re going to try to memorize. You simply need to know where you can
access this stepped-up program for readministering or restarting IMDELLTRA®.
25:26
Dr David Waterhouse, MD: IMDELLTRA® dosing and administration. This is a drug that’s going
to be
administered in an appropriate healthcare setting as a 1-hour IV infusion every two weeks.1 And
we talked
about that stepped-up dosing.1 This is that day one, day eight strategy that we saw for that
first cycle.1
And then we go to every other week strategy.1 And again, you’re going to have to observe these
patients post
infusion.1 So they are going to be your patients who you bring in in the morning, get them dosed,
just keep
an eye on them.1
26:01
Dr David Waterhouse, MD: So the safety warnings, I said they’d be peppered out in the deck. This is
true of
all the decks that you guys look at. Neurologic toxicity, ICANS, we talked about this earlier. Again, it can
be a serious or life-threatening toxicity.1 So you have to be able to recognize it and you have
to be able
to manage it. About 10% of the patients will be Grade 3.1 More often than not this presents as a
headache,
but it could be peripheral neuropathy, dizziness, insomnia, muscle weakness, and other
toxicities.1 It
occurred in 9% of the treated patients and it was recurrent in 1.6% of the patients.1 Most of
them
experienced it following Cycle two Day one (24%).1 So this is going to occur later in the
treatment than
what we saw with the CRS.1 It can occur concurrent with CRS.1 So these are not
mutually exclusive.1 It can
occur following CRS or even in the absence of CRS.1 This is its own side effect and patients are
at risk for
neurologic adverse events as a result of this.1
27:09
Dr David Waterhouse, MD: It can result in a depressed level of consciousness.1 So we do
need to
advise to
our patients to refrain from driving or engaging in hazardous occupations or activities, heavy lifting and
things, in the event of any of their neurologic symptoms, and certainly going to wait until they resolve
completely and closely monitor the patients for the signs and symptoms of neurotoxicity.1 I
mentioned
earlier the importance of the teaching sessions before we start treatment with our patients. We talked about
CRS teaching, now we’re talking about neurologic teaching and it’s important to also engage the patient’s
caregivers and families and loved ones as we do this. It takes a team to manage these patients and that’s
okay. Now you don’t have to think you have to do this all alone. There are resources out there available for
patient counseling and other resources. All of our patients really deserve the opportunity to have access to
these cutting-edge therapies. Amgen has a lot of support that they can make available to you as the provider
and to the patients and their families. You can call Amgen; you can go to their website. They have a
healthcare provider support center; they have patient navigators and other resources that they can bring to
help our patients get these treatments.
28:38
Dr David Waterhouse, MD: Other support services include financial support and co-pay assistance.
Again, do
not hesitate or be fearful of reaching out to Amgen, who also wants to see your patient get the same degree
of care that you want them to get. Going back again to the important safety information. So managing
toxicity is so important. So let’s just go again, talk about it just for another second more. The indication
we’ve already talked about—those patients with extensive-stage small cell [cancer] with disease progression
on or after platinum-based therapy.1 We talked about [how] we don’t need any biomarkers, we just
need to
have progressed.1 And when we talk about important safety information, let’s go back to cytokine
release
syndrome and neurologic toxicity, which includes the ICANS neurotoxicity syndrome. Cytokine release
[syndrome] can be life-threatening.1 [It] tends to occur earlier in the patients.1 We
can help prevent some
of that using that stepped-up dosing and that’s strongly encouraged.1 And you’re going to hold if
you get
this until it resolves and in a few of the patients you may have to discontinue if the severity is high
enough.1
29:50
Dr David Waterhouse, MD: Neurologic toxicity including ICANS can also be serious and you’re going to
monitor
for signs and symptoms of neurologic toxicity and you’re going to get on it early.1 You’re not
going to wait
until they’re in trouble, and you will withhold and sometimes even stop it for the treatment based on that
level of toxicity (the grading that we talked about earlier).1
30:15
Dr David Waterhouse, MD: More on cytokine release syndrome. So we talked about [how] this occurs in
55% of
the patients, so you’re going to have to tell them more than half are going to get this side
effect.1 Most
of it early grade including 34% Grade 1, 19% Grade 2, only 1.1% Grade 3, and 0.5% Grade 4.1 And
if you’ve
had it once, there’s a 24% chance you’re going to get it again when you’re retreated. And that usually is
low-grade toxicity, 18% of it being Grade 1, 6%, I’m sorry, being Grade 2.1
30:53
Dr David Waterhouse, MD: And almost all of these events are occurring after that first dose, 43% on
the
first dose, 29% of the patients are going to experience it on the second dose and only 9% of the patients
experiencing it following the third dose or later.1 So it’s an early toxicity and you can see the
numbers as
we’ve gone along. We’ve been talking about this. Remember, CRS is characterized by fever, hypotension,
fatigue, tachycardia, headache, hypoxia, nausea, vomiting.1 Okay, so again, you’re going to
identify that
the patient has the toxicity. You are going to grade the toxicity using the grading scale that we presented
earlier. Based on that grade, you’re going to intervene following the algorithms that are given to
you.1 We
can say the same thing for neurologic toxicity. It can also be severe. It occurred in 47% of the patients
and about 10% of them had Grade 3 neurotoxicity.1
31:55
Dr David Waterhouse, MD: Again, headache, peripheral neuropathy, dizziness, insomnia, muscle
weakness.1 You
need to identify these patients and if you choose to treat them again, again, the ICANS occurred in 9% of
the patients and if you treat them again, it’s recurrent in 1.6% of the patients.1 Now here we
saw that it
occurred a little bit later than we saw with CRS, and we talked about that earlier, and it is an independent
event.1 It can occur with CRS.1 It can occur following the resolution of
CRS.1 It could occur even if the
patient didn’t have CRS.1 Once again, you’re going to identify the patient. You’re going to grade
the
patient.1 You’re going to follow the management algorithm, and you’re going to support the
patient.1 You
notice that this is sort of a recurrent theme. Cytopenias—I think most of us are very comfortable managing
cytopenias in patients with small cell lung cancer.
32:56
Dr David Waterhouse, MD: All those of us who grew up giving all these patients chemo know how to
manage that
disorder. Infections largely are a result of the treatment that caused cytopenias and they can include
opportunistic infections.1 Infections were seen in 41% of the patients who received
IMDELLTRA®
with Grade 3
or Grade 4 infections occurring in 13%.1 Now given the era that this trial was done, the most
frequent
infection was COVID with 9% of the patients.1 But remember this was during the pandemic followed
by UTIs
(10%), pneumonia, (9%), other respiratory infections and candida, infections were at 3.2%.1 We’re
going to
monitor our patients for signs and symptoms of infection.1 We’re accustomed to doing that.
33:49
Dr David Waterhouse, MD: Hepatotoxicity can be seen.1 Elevated ALTs were seen in 42%,
Grade 3,
Grade 4
hepatotoxicity, 2.1%.1 Same thing with AST elevations occurring, bilirubin 15%.1
Again, we’re accustomed to
seeing liver toxicity. Hypersensitivity reactions—they’re not terribly common, but again, you’re going to
withhold and manage them like you do other hypersensitivity reactions,1 and based on the mechanism of
action, you would expect that there could be embryo fetal toxicity.1 And let’s be hopeful that we
never put
ourselves in that position. Going back to the most common adverse events, when we do our teach, we’re going
to talk about CRS occurring in 55%, fatigue, (51%), well third-line small cell, that’s not a surprise,
fever, (36%), dysgeusia, (36%) decreased appetite (34%), and the list goes on down that line.1
These are
teaching opportunities. As we’re meeting with our patients before we get going, we’re going to tell them
that side effects will occur, but that we know how to manage them.
35:05
Dr David Waterhouse, MD: Serious adverse events occurred in 58% of the patients.1 SAEs
were
greater than 3%
included CRS (24%), pneumonia (6%).1 And again, we can go down that line and look at this. These
are all
things that we’ve talked about. The dosing administration we talked about earlier. This is a 1-hour
infusion.1 There is a stepped-up dosing strategy that you want to be familiar with.1
There are concomitant
medications and pre-medications.1 You want to do this in a center where you would normally be
doing your
infusions, and you have to be cognizant of CRS and neurologic toxicity and be prepared to manage that in the
event that you encounter it.1 You’re going to follow blood counts, you’re going to follow their
CMP
[comprehensive metabolic panel].1 You do this in all of those patients, and you want to make sure
that the
patient is well hydrated.1 Again, all of this information can be found in the prescriber
information
including the boxed warnings.
36:13
Dr David Waterhouse, MD: Okay, so this is the overview slide, the money slide. So
IMDELLTRA® is the first
and only DLL3-targeting BiTE® therapy for adult patients with extensive small cell and disease
progression
after a platinum-based chemotherapy.1 And it’s going to activate the patient’s own T cells to
attack these
DLL3-expressing cells.1 And remember, the great majority of the patients will have these
expressing cells,
so we don’t have to worry about getting a biomarker.1,6,7 The DeLLphi-301 trial was a phase 2
open-label,
multicenter, multi-cohort trial evaluating IMDELLTRA®,1,2 and we’re looking at the response rates
in 99
patients who were treated with disease progression after a platinum-based chemotherapy and at least one
other line of therapy.1 And with that, the overall response rate was 40%.1 The median
duration of response,
9.7 months.1 And among those who responded to IMDELLTRA®,1,2 the majority, (68%) of
those responded for
greater than six months and 40% still responding at one year.1
37:24
Dr David Waterhouse, MD: Safety and tolerability was evaluated in 187 patients with extensive disease
with
the most common adverse reactions associated with IMDELLTRA® occurring in greater than 20% of the
patients
CRS, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, nausea,
and also IMDELLTRA® was associated with immune mediated AEs such as CRS and ICANS, which are
included in the
boxed warnings for this product.1 You’re going to want to administer it in an appropriate
healthcare
setting, 1-hour infusion every two weeks after of course you do the initial stepped-up dosing schedule to
reduce the incidents and severity of the CRS.1 So this brings my presentation to a close and I
really want
to thank all of you for letting me and giving me the privilege of presenting this opportunity for all of
your patients with extensive-stage, previously treated small cell lung cancer.1 At this point, on
the
right-hand side of your slides, you can see a QR code if you want to learn more about IMDELLTRA®
or if you
want to visit their website. Likewise, you can visit the Amgen support website listed there. We know that
there’s questions and we want to get to those, and I believe the program is going to be closed out by my
colleague Byeong Yoon.
38:51
Byeong Yoon, PhD: Thank you Dr Waterhouse, for that wonderful thorough presentation on
IMDELLTRA®. I think
now it’s time to transition into the Q&A and there have been some questions submitted via the chat. The
first question is actually regarding the phase 3 confirmatory trial. So the question is, what is the status
of the IMDELLTRA® confirmatory phase 3 trial, and what are the endpoints that are being studied?
Dr
Waterhouse?
39:16
Dr David Waterhouse, MD: Sure! IMDELLTRA® is currently being studied in the DeLLphi-304
study, which is an
ongoing confirmatory phase 3 trial in relapsed small cell lung cancer versus standard of care
chemotherapy.12 The primary endpoint of this study though is overall survival, and select
secondary
endpoints include progression-free survival and duration of response.12
39:40
Byeong Yoon, PhD: Thank you Dr Waterhouse. Now there’s a second question, and I think we anticipated
this
based on what we know about IMDELLTRA®. So regarding the operationalization and the
considerations for that.
And the question is, what operationalization considerations should my staff and I keep in mind for when I
prescribe IMDELLTRA® to my patients with extensive-stage small cell lung cancer? Dr Waterhouse,
given your
experience, maybe I can hand this over to you.
40:05
Dr David Waterhouse, MD: Well, thank you again. It’s important that your staff and you feel both
equipped
and confident in your decision to treat your patient with IMDELLTRA®. And with that, there are
considerations to be aware of regarding IMDELLTRA® preparation, administration, management of
potential
adverse reactions, and all of this is outlined in the US Prescribing Information. So, the preparation of
IMDELLTRA® required materials such as Sterile Water for Injection for the reconstitution of
IMDELLTRA®, and
0.9% Sodium Chloride for the Injection in preparation of the IV bag.1 And the administration will
require an
infusion pump that’s programmable, lockable, non-elastomeric, and has an alarm.1 It’s also
important to note
that IMDELLTRA® should only be administered by qualified healthcare professionals in a setting
that’s
equipped with the appropriate medical support to manage potential adverse events such as CRS and neurologic
toxicity, including ICANS, and cytopenias, infections, other adverse reactions.1 Medical support
may include
necessary access to an ICU facility, including telemetry, neurologists and neuroimaging capabilities, and of
course medications such as tocilizumab.1 Other important monitoring requirements might include and followed
by the US PI. You can visit IMDELLTRAhcp.com. You can look at the full Prescribing Information provided
during the presentation to learn more.
41:41
Byeong Yoon, PhD: There’s a third question that’s coming, maybe Dr Waterhouse if you want to cover
and I can
maybe address it.
41:48
Dr David Waterhouse, MD: Sure. Well, this one’s pretty simple. When will IMDELLTRA® be
available so that I
can prescribe it to my patients and how can I order it?
41:59
Byeong Yoon, PhD: And the good news is IMDELLTRA® is available to order via your specific
specialty
distributor and you can call their toll free number or visit their website.1 Now, if you don’t
know which
specialty distributor to call on, within the IMDELLTRA® Product Fact Sheet, which is available
for download
on IMDELLTRAhcp.com, there is a list of specialty distributors available there.
42:24
Dr David Waterhouse, MD: Can you explain in more detail the role of the Amgen Patient Navigator and
how will
they work with both physicians and patients?
42:33
Byeong Yoon, PhD: Now thank you. And Dr Waterhouse covered some of the services provided by Amgen for
IMDELLTRA®, and one of them is the Amgen Patient Navigator. And we see the Amgen Patient
Navigator as a
single point of contact to help answer questions about access, reimbursement, navigating the treatment
logistics, and to provide any supplemental resources as patients transition from hospital to outpatient
care. Now, Patient Navigators can support both offices and patients alike and are part of Amgen SupportPlus
program, and they can help patients and offices navigate the IMDELLTRA® treatment journey. Now, I
do want to
remind Amgen Patient Navigators are not part of your patient’s treatment team and cannot provide medical
advice, nursing, or case management services. They cannot administer Amgen medication, and patients should
always consult their healthcare provider regarding medical decisions or treatment concerns. You can find
more details around the Patient Navigators by visiting amgensupportplus.com. And once you are in touch with
someone at Amgen SupportPlus, they will connect you with a geographically specific Patient Navigator for
support. So the next question is actually I think something that maybe Dr Waterhouse, I’ll ask you to cover
and answer. So understanding some teams will be new to CRS and this is related to that. So the question here
that came in is, my team is new to CRS and ICANS. What resources does Amgen have that I may be able to
access to educate my staff and themselves?
44:14
Dr David Waterhouse, MD: Well, that’s a great question. Within IMDELLTRA®: Cytokine
Release Syndrome (CRS) &
Neurologic Toxicity/ICANS Management Guide, you can actually find the information on CRS and ICANS grading,
incident rates, and clinical trials, signs and symptoms information, monitoring requirements, and management
strategies including dose modifications. You can also refer to the full US Prescribing Information for more
details.
44:40
Byeong Yoon, PhD: Okay, now, thank you for that, Dr Waterhouse. Now, I think the other questions
[are]
around some of the resources are available regarding to access. And so the question asks, what access
support resources are available to patients who are prescribed IMDELLTRA®, Dr Waterhouse?
44:58
Dr David Waterhouse, MD: Oh, it is the utmost importance to Amgen to help patients who are prescribed
in
IMDELLTRA® have the support needed to access this treatment. For many patients
IMDELLTRA® may be covered by
their insurance. However, coverage differs by healthcare plan. You can contact Amgen SupportPlus by either
the phone or going to the website, and you can review your patient’s insurance and other coverage options if
applicable. And for those of your patients with Medicare Advantage, these plans generally cover all of the
treatments that traditional Medicare Fee For Service covers. As mentioned, coverage may differ by health
plan, and Amgen SupportPlus can help review your patient’s insurance and other coverage options if
applicable.
45:42
Byeong Yoon, PhD: Well, thank you Dr Waterhouse, for your wonderful presentation. And thank you for
answering some of the questions that’ve come in. I think as Dr Waterhouse highlighted, and I think as we all
recognize, extensive-stage small cell lung cancer really represents a disease with a high unmet need.3 We
believe that approval of IMDELLTRA® represents a pivotal moment for patients with this disease,
and Amgen is
privileged to bring this innovative breakthrough treatment for patients with extensive-stage small cell lung
cancer.1 As we celebrate this moment for patients, we want to thank all the investigators, the patients, and
the families who partnered with us to bring IMDELLTRA® to patients with extensive-stage small
cell lung cancer. At Amgen, our hope moving forward is that we can continue to bring new meaningful treatment options
and hope for our patients, their loved ones, and their care teams. On behalf of Amgen, I want to first thank
Dr Waterhouse, and thank you all for being with us this evening and thank you all for what you do for your
patients. With that we’ll close our program. Goodnight.
