August 14, 2023 • 41 mins
In a new episode of The Onco'Zine Brief, Peter Hofland talks with David M. Cognetti, MD, a Professor and Chair in the Department Head and Neck Surgery at Thomas Jefferson University Hospital in Philadelphia.
Hofland and Cognetti talk about head and neck cancer and a novel treatment approach called Photoimmunotherapy.
Head and Neck Cancer
According to the American Cancer Society, Head and neck cancer accounts for about 4% of all cancers in the United States. In the United States in 2023, an estimated 67,000 people will be diagnosed with head and neck cancer and about 15,000 patients are expected to die of the disease.
Today, many cancers of the head and neck can be cured, especially if they are found early. And while eliminating the cancer is the primary goal of treatment, preserving the function of the nearby nerves, organs, and tissues is also very important.
Beyond Current Treatment
Photoimmunotherapy is a recently developed hybrid cancer therapy to treat diseases by linking specific antibodies with photosensitizers to form photoimmunoconjugates.
But let’s go back to the beginning.
Surgery, radiation, and chemotherapy have dominated the treatment of oncologic. These therapies aim to eradicate cancer cells but, unfortunately, do that at the expense of normal, or healthy cells/ In turn, this can lead to severe and sometimes lethal side-effects.
Overall, the success of surgery, radiation and chemotherapy is measured by what we call a ‘therapeutic index.’
This ‘therapeutic index’ compares the potential benefits of treatment to the potential risks associated with treatment.
Unfortunately, the unintended, off-target side effects of these therapies can have profound effects on the health-related quality of life of patients.
For example, both radiation and chemotherapy sometimes preferentially kill lymphocytes much earlier than cancer cells because of the increased radiation sensitivity and high proliferation rate of lymphocytes, potentially leading to dose-limiting toxicity for some chemotherapy regimens.
To find a solution, researchers have developed new therapeutic strategies. And while these therapies have created an exciting new direction for the treatment of cancer therapy, there remain limitation to these novel approaches.
Now, in theory, the perfect cancer therapy would both directly destroy cancer cells to minimize residual cancer cells as well as activate the local host immune response to wipe out remaining cancer cells.
And while such a therapy would be highly selective for cancer cells but have minimal or no off-target effects in the tumor microenvironment.
Photoimmunotherapy
And that’s where photoimmunotherapy comes in. Photoimmunotherapy, designed to selectively destroy target cells.
The therapy that induces direct cancer killing via immunogenic cell death, thus activating the anti-cancer immune system locally in the tumor microenvironment.
The specificity of this approach comes from the antibody that is designed to target an expressed antigen on the tumor surface and is conjugated to the photo-activating chemical.
The safety of Photoimmunotherapy is based on the fact that the antibody–photo-absorber conjugate predominantly binds to specifically targeted cancer cells and that it is only activated in areas exposed to Near-infrared light at a specific activating wavelength.
By choosing tumor-specific antigens, this therapy specifically destroys cancer cells while not or only minimally harming any adjacent normal or healthy cells, particularly tumor-infiltrating immune T cells or blood vessels. Furthermore, the photo-activating chemical is a water-soluble photo-absorbing dye without cytotoxic properties of its own.
Clinical studies have shown that this combination can enhance the immune response, and, as a result, have a good effect on the treatment of residual tumor and metastatic cancer.
The first human study of a Photoimmunotherapy was with ASP-1929 – which is being developed by Rakuten Medical to treat inoperable head and neck cancer.
ASP-1929 is a conjugate of cetuximab, an anti-EGFR antibody plus the photo-absorber called IR700.
About The Onco'Zine Brief
The Onco'Zine Brief is distributed in the United States via PRX (Public Radio Exchange). In the United Kingdom and Europe, the program is distributed via UK Health Radio (UKHR). And the program can be downloaded via most podcasts and streaming media services, including iTunes, Spotify, TuneIn, and iHeart Radio.
For more information about The Onco'Zine Brief or how to sponsor or support this public radio broadcast and podcast, visit to downl
Hofland and Cognetti talk about head and neck cancer and a novel treatment approach called Photoimmunotherapy.
Head and Neck Cancer
According to the American Cancer Society, Head and neck cancer accounts for about 4% of all cancers in the United States. In the United States in 2023, an estimated 67,000 people will be diagnosed with head and neck cancer and about 15,000 patients are expected to die of the disease.
Today, many cancers of the head and neck can be cured, especially if they are found early. And while eliminating the cancer is the primary goal of treatment, preserving the function of the nearby nerves, organs, and tissues is also very important.
Beyond Current Treatment
Photoimmunotherapy is a recently developed hybrid cancer therapy to treat diseases by linking specific antibodies with photosensitizers to form photoimmunoconjugates.
But let’s go back to the beginning.
Surgery, radiation, and chemotherapy have dominated the treatment of oncologic. These therapies aim to eradicate cancer cells but, unfortunately, do that at the expense of normal, or healthy cells/ In turn, this can lead to severe and sometimes lethal side-effects.
Overall, the success of surgery, radiation and chemotherapy is measured by what we call a ‘therapeutic index.’
This ‘therapeutic index’ compares the potential benefits of treatment to the potential risks associated with treatment.
Unfortunately, the unintended, off-target side effects of these therapies can have profound effects on the health-related quality of life of patients.
For example, both radiation and chemotherapy sometimes preferentially kill lymphocytes much earlier than cancer cells because of the increased radiation sensitivity and high proliferation rate of lymphocytes, potentially leading to dose-limiting toxicity for some chemotherapy regimens.
To find a solution, researchers have developed new therapeutic strategies. And while these therapies have created an exciting new direction for the treatment of cancer therapy, there remain limitation to these novel approaches.
Now, in theory, the perfect cancer therapy would both directly destroy cancer cells to minimize residual cancer cells as well as activate the local host immune response to wipe out remaining cancer cells.
And while such a therapy would be highly selective for cancer cells but have minimal or no off-target effects in the tumor microenvironment.
Photoimmunotherapy
And that’s where photoimmunotherapy comes in. Photoimmunotherapy, designed to selectively destroy target cells.
The therapy that induces direct cancer killing via immunogenic cell death, thus activating the anti-cancer immune system locally in the tumor microenvironment.
The specificity of this approach comes from the antibody that is designed to target an expressed antigen on the tumor surface and is conjugated to the photo-activating chemical.
The safety of Photoimmunotherapy is based on the fact that the antibody–photo-absorber conjugate predominantly binds to specifically targeted cancer cells and that it is only activated in areas exposed to Near-infrared light at a specific activating wavelength.
By choosing tumor-specific antigens, this therapy specifically destroys cancer cells while not or only minimally harming any adjacent normal or healthy cells, particularly tumor-infiltrating immune T cells or blood vessels. Furthermore, the photo-activating chemical is a water-soluble photo-absorbing dye without cytotoxic properties of its own.
Clinical studies have shown that this combination can enhance the immune response, and, as a result, have a good effect on the treatment of residual tumor and metastatic cancer.
The first human study of a Photoimmunotherapy was with ASP-1929 – which is being developed by Rakuten Medical to treat inoperable head and neck cancer.
ASP-1929 is a conjugate of cetuximab, an anti-EGFR antibody plus the photo-absorber called IR700.
About The Onco'Zine Brief
The Onco'Zine Brief is distributed in the United States via PRX (Public Radio Exchange). In the United Kingdom and Europe, the program is distributed via UK Health Radio (UKHR). And the program can be downloaded via most podcasts and streaming media services, including iTunes, Spotify, TuneIn, and iHeart Radio.
For more information about The Onco'Zine Brief or how to sponsor or support this public radio broadcast and podcast, visit to downl
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:12):
This is The Youngazine Brief with PeterHoffland. Welcome to a new episode of
The Angasine Brief. I'm Peter Hofland, and in this episode of the program,
I'll be talking with doctor David Coocknetti, a professor and chair in the
Department of headen Neck Surgery at ThomasJefferson University Hospital in Philadelphia. In this
(00:34):
episode, we talk about head andneck cancer and a novel treatment approach called
photo immunotherapy. According to the AmericanCancer Society, head and neck cancer accounts
for approximately four percent of all cancersin the United States and in twenty twenty
three, this translates to approximately sixtyseven thousand people who will be diagnosed with
(00:54):
head and neck cancer and about fifteenthousand patients who are expected to die of
the disease. Today, many cancersof the head and neck can be cured,
especially if they are found early andWhile eliminating the cancer is the primary
goal of treatment, preserving the functionof the nearby nerves, organs, and
tissue is also very important and iswhere photoimmunotherapy may start a player role.
(01:19):
Photoimmunotherapy is a recently developed hybrid cancertherapy to treat cancers by linking specific antibodies
with photosynthesizers to form photoimmunoconjugates. Butlet's go back to the beginning. Surgery,
radiation, and chemotherapy have dominated thetreatment of oncology. These therapies aim
to eradicate cancer cells, but unfortunatelyoften do that at the expense of normal
(01:42):
or healthy cells. In turn,this can lead to severe and sometimes lethal
side effects. Overall, the successof cancer therapy, including surgery, radiation,
and chemotherapy are measured by what wecall a therapeutic index. This therapeutic
index compare the potential benefits of treatmentto the potential risk associated with these treatment.
(02:05):
Unfortunately, the unintended off target sideeffects of these therapies can have profound
effects on the health related quality oflife of patients. For example, boat
radiation and chemotherapy sometimes preferentially kill lymphocytesmuch earlier than cancer cells. This happens
because of the increased radiation sensitivity andhigh proliferation rate of lymphocytes, potentially leading
(02:28):
to those limiting toxicities for some treatmentregiments. To find the solution, researchers
have developed new therapeutic strategies, andwhile these therapies have created new and exciting
directions for the treatment of cancer.They remain limitations to these novel approaches.
Now, in theory, the perfectcancer therapy would bote directly destroy cancer cells
(02:50):
to minimize residual cancer cells, aswell as activate the local host immune response
to wipe out remaining cancer cells,and such a therapy would be highly selective
for cancer cells but have minimal orno off target effects in a tumor micro
environment, and that is where photoimmunotherapycomes in. Photoimmunotherapy is designed to selectrically
(03:14):
destroy cancer cells. This therapy indusesdirect cancer killing via immunogenic cell death,
thus activating the anti cancer immune systemlocally in the tumor micro environment. The
specificity of this approach comes from theantibody that is designed to target an expressed
antigen on a tumor surface and isconjugated to a photoactivating chemical. The safety
(03:36):
of photoimmunotherapy is based on the factthat the antibody photoactivating chemical conjugate predominantly binds
to specifically targeted cancer cells and thatit is only activated in areas exposed to
near infrared light at a specific activatingwavelength. By choosing tumor specific antigens.
This therapy specifically destroys cancer cells,while not or only minimum harming any adjacent's
(04:00):
normal or healthy cells, particularly tumorinfiltrating immune T cells or blood vessels.
Furthermore, the photo activating chemical isa water soluble photo absorbing dye with outside
the toxic properties of its own.Clinical studies have shown that this combination can
enhance the immune response and as aresult, have a good effect on the
(04:23):
treatment of residual tumor and metastatic cancer. The first human study of a photo
immunotherapy was with ASP nineteen twenty nine, which is being developed by Racket and
Medical and is used for the treatmentof inoperable head and neck cancer. ASP
nineteen twenty nine is a conjugate ofstoximab, an anti eedfr antibody plus the
(04:44):
photo absorber or photo activating chemical calledR seven hundred. I'm Peter Hoffland and
this is the Youngosine Brief. TheYoungesine Brief is developed in collaboration with our
online journal on Coosine, where youcan find additional information in the latest news
about cancer, cancer diagnosis and treatment, and cancer prevention. For more information
on how to support this program,visit our website at oncozine, and if
(05:09):
you're living in the United States andwant to receive our newsletter, text the
word cancer to six six eight sixsix and we will make sure that you'll
receive our newsletter, which includes anoverview of the latest news in oncology and
hematology. This is the Ongazine Brief. For the latest news about cancer and
(05:34):
cancer treatment, visit our online journalOncazine at www dot kazine dot com.
On the phone with me is doctorDavid Cocknetti. Doctor Cocknetti is a professor
and chair in the Department of Headand Neck Surgery at Thomas Jefferson University Hospital
in Philadelphia. Doctor Cocknetti, welcometo the Angasine Brief. Now, before
(05:56):
we come to talk about photo immunotherapyand some very interesting data and results presented
at this year's annual meeting of theAmerican Head and Next Society, tell me
a little bit more about yourself andhow you got here. So I'm David
Agnetti, as you've already recognized,I'm a head neck cancer surgeon. I'm
based out of Thomas Jefferson University inPhiladelphia, and I got interested in treating
(06:19):
patients with headnet cancer. Going backto my training years in medical school at
the University of Pittsburgh, I wasexposed to doctor Jean Myers and Jonas Johnson
and others that really introduced me tothe field. And when I did my
residency training at Jefferson, which iswhere I ended up long term, it
(06:41):
just solidified that these were the patientsthat I wanted to help care for throughout
my career. Now, head andneck cancers are very difficult to treat.
Can you give me a little bitbackground how these cancers are treated today?
And in additionally, why is thisdisease so difficult to treat? That's an
excellent question. Headnet cancer is difficultto treat for a couple of reasons.
(07:04):
Number one is the anatomy that itimpacts. If you think about it,
your face and your head neck.That's your presentation of the world. So
not only is it your appearance,but it's also the area of many of
our most vital functions communicating, breathing, eating, So headnet cancer or the
(07:26):
treatments to cure it or try tocure it, have impact on all of
those vital functions and a person's presentationof the world, So it can be
very devastating for the patient. Interestingly, headnet cancer has evolved over the last
twenty years. I just gave youmy background of what made me interested in
it. When I was first startingoff in medical school, the only or
(07:49):
the major causes of headnet cancer weresmoking, tobacco or any use of tobacco
and alcohol. And now fast forward, a major cause and the biggest driver
of oral forngeal cancer or throw canceris HPV human papalona virus. And so
(08:11):
we've seen a shift in the typesof patients we're seeing and at the same
time, we've had major shifts intreatment options for these patients. So it's
as devastating as it can be asa disease, it's still a very exciting
time to be in the business ofcaring for this disease. Let's take a
break. This is the Younger ShameBraef. If you're just joining us.
(08:35):
In today's episode of The Younger ShameBraef, I'm talking with doctor Davis Cocknetti.
Doctor Cocknetti is a professor and chairin the Department of Head and Neck
Surgery at Thomas Jefferson University Hospital inPhiladelphia. In this episode, we talk
about the development of photoimmunotherapy and headand neck cancer. I'm Peter Hoffland and
this is the younger shim Braef.Each day, researchers make new discoveries that
(09:07):
bring us closer to the moment whenall cancer patients can become survivors. Some
days they take small steps, others, huge discoveries lead to giant leaps forward.
This progress, both small steps andgiant leaps, happens with the health
of clinical trials. Clinical trials area fundamental path to progress and the brightest
(09:28):
torch researchers have to light their waytowards better treatments, and if you've been
diagnosed with cancer, they may beyour brightest ray of hope. Clinical trials
introduce new hope in addition to thecurrent standard of care by allowing researchers to
provide participants access to cutting edge andpotentially life saving treatments. So if you're
(09:48):
interested in exploring new treatment options whilehelping to light the path for other patients,
clinical trials may be the best choicefor you. Speak with your doctor
and visit stand Up to cancer dotorg slash clinical trials to learn more about
clinical trials. Together, we canstand up for all of us This is
(10:13):
the Young Gazine Brief with Peter Hofflandand welcome back. This is the Younger
Him Brief. If you're just joiningus in today's episode of The Angus Him
Brave. I'm talking with doctor DavidCoocknetti. Doctor Cocknetti is professor and chair
in the Department of Head and NeckSurgery at Thomas Jefferson University Hospital in Philadelphia.
(10:39):
So, during the recent annual meetingfrom the American Society of Clinical Oncology
or ASCO, they were presentations talkingabout these transitions from smoking related head and
neck cancer. If I recall correctlyto HPV, those two forms of cancer,
how different are they? For example, when you have a patient that
is diagnosed with head and neck cancerthat is caused by smoking, or you
(11:01):
have a patient has been diagnosed withheadoneck cancer links to HPV associated with oral
sex, how different are those formsof cancer. They're very different, both
the cancer itself, the prognosis forthe cancer self is different, and the
people who get them, the riskfactors that lead to it. So the
traditional headneck cancer caused by smoking anddrinking is generally an older generally occur as
(11:28):
an older gentleman who have a lotof other comorbidities caused by smoking, So
if they were to survive their cancer, oftentimes they don't have a very good
overall survival because they're the ones whoare getting heart attacks and strokes and other
things that are also caused by smoking, lung cancer, etc. And on
(11:50):
top of that, of the twocancer types, it's a much harder one
to cure the ones that are notrelated to HPV. Now, the ones
that are related to HPV that happensnow in younger people who have never smoked.
So when it first came on thescene was a little confusing, why
are these people getting cancer? Nowwe have a very clear understanding of why
(12:13):
they're getting the cancer, but it'sin people who don't have the other commorabilities
caused by smoking. So if youtake instead of a sixty five year old
person, you have a forty fiveyear old person, And instead of somebody
who's at risk of heart attack,lung cancer, and stroke, you have
somebody who is a very healthy person. And now you add on that they
(12:35):
are more likely to be cured.Well, you have to count now that
they're going to be around for decadesinstead of the other type where they generally
wouldn't live for decades. So howwe treat these patients keeping in mind their
functional outcomes over the years is veryimportant. And if you look at the
available treatment options for a patient thatis diagnosed with head the neck can are
(13:00):
linked to smoking or head neck cancerlinked to HBV and oral six in i
a case, what is the currentstandard therapy and the best treatment options for
those cancers? Cancer? In general? The treatment options are any combination of
surgery, radiation and chemotherapy. Arethose are the very traditional one And what's
(13:22):
interesting we say headnet cancer, butheadnet cancer is actually a collection a bunch
of smaller subsite cancers. And whatI mean by that, although we bucket
them into headnet cancer, and althoughthey're almost always scream as cell cancer which
is the surface cell, the tonguecancer or oral tongue cancer, the front
end of the tongue behaves very differentlythan base of tongue cancer. The back
(13:46):
of the tongue behaves very differently thanlarynx cancer. The voice box behaves differently
than hypofarings cancers, so and nasopharingx cancer. They're all individually have different
treatment algorithms and agnoses. In someof them, for example, the oral
cavity surgery is the preferred treatment,and some of them, for example,
the nasal farings, radiation and chemotherapies of preferred treatment. So it's different
(14:11):
depending on the exact subsite, whichis only centimeters away from each other,
and based on what you said earlierin this program, surgery may be difficult
because it is such a complex,anatomical and very congested area, right,
So tell me a little bit moreabout this in case surgery is needed.
It's very complex and difficult, right. It's anatomically complex and it's functionally important.
(14:35):
So yes, those two things addup for making surgery difficult, and
unfortunately, there's been advances on howwe do surgery with a higher prioritization in
modern day surgery compared to the paston making sure we account and preserve function.
Now, when you look at thefield today and you look at the
(14:56):
options for treatment, the kind ofpatient that you're dealing with, what would
you say are some of the unmetmedical needs that patients are facing in terms
of the availability of treatment options andlimitations to treatment for patients you may not
be able to treat. What aresome of the issues that you're encountering you
practice today, so unmet needs.There are still many of these patients that
(15:18):
are not being cured. So numberone priority is to improve the cure rate.
And then we've touched on a numberof times here how destructive our current
treatments can be to the function ofthe patient. So if you're doing surgery,
you're cutting out tissue, and soeven if it replaces the non functional,
(15:41):
radiation has long term devastation on thenormal tissue, causes fibrosis, it
stiffening of the tissue, it causesdry mouth and zerostomia, and really ruins
the normal tissue. And chemotherapy canhave acute toxic effects and make the effects
(16:02):
of radiation that the side effects evenworse. So wrapped up in all of
that, there's plenty of room forimprovement on both curing these patients and curing
them with their highest quality of lifebecause again, the location and the impact
of this cancer and the treatments ofsignificant manifestations on quality of life. Now
(16:26):
you've been working and treating patients forquite some time. If you look back
at studies presented at different medical andclinical meetings from the American Society of Clinical
Oncology, the American Association of CancerResearch and the American Head and Neck Society,
and maybe some other meetings. Thereis still the question that are here
often are there any new treatment optionsfor head and neck cancer coming out?
(16:48):
Are there new things available? Incontrast, for example, if you look
at breast cancer, treatment options forhead and neck cancer seems to be very
slow incoming. Later in our program, we'll be talking a little bit about
photo immunotherapy and the results of ongoingstudies you've been involved with. Some of
these developments have been in development fora long time. But tell me,
(17:11):
other than the complexities of the diseaseitself, which we talked about, are
there other reasons why it is sodifficult to develop new treatment options or why
is the field moving so slowly?That's a great question. I think you
could look at the field almost dichotomously, and what I mean by that is
in recent years, it seems likethings are really speeding up in new discovery,
(17:33):
new options ofmunotherapy, and what we'reseeing across cancer care in general.
But you're right, if you takea broader picture view and step back,
it's been slow advance, very slowmovement of the needle in terms of overall
survival for these patients. With thebiggest impact on survival and headnet cancer is
(17:55):
probably the virus itself, human papulomavirus. By more of the cancer being
related to human papuloma virus, thatin turn has improved survivorability. Not necessarily
that our treatments got better. Wewere just treating a better prognosis disease.
So you're right. So part ofit is that's what it takes to develop
cancer care treatments. Part of itis when new exciting things come on,
(18:21):
we do have to carefully study themin a way that doesn't put at risks
the patients and the gains that havealready been made. And so you know,
clinical trials of the appropriate design andpower take time, They take years
to report out. Let's take abreak. This is the Young Mashine Brief.
(18:41):
If you're just joining us in today'sepisode of the Young Mashine Brief,
I'm talking about doctor David Cooknetti.I'm Peter Hoffland, and this is the
Young Mashine Brief. Odds are you'venever heard that word before, but for
(19:03):
the forty people diagnosed with sarcoma everyday, it is a life changing word,
life changing and devastating because sarcoma iscancer. Sarcoma is a cancer of
bone and soft tissue, more prevalentin children than in adults. More than
six thousand people lose their lives tosarcoma each year. Treatment options for sarcoma
are limited, and new therapies aredesperately needed. More research and increased awareness
(19:27):
is necessary to find a cure fora cancer that you probably didn't even know
existed until now. Through awareness,advocacy, and research, the Sarcoma Foundation
of America is determined to help thoseaffected by this forgotten cancer. To bring
hope to the children and adults whoselives are forever changed by a word they
had never heard before. Please helpus in the fight to find the cure
(19:49):
for sarcoma. For more information onsarcoma and the work of the Sarcoma Foundation
of America, please go to CureSarcoma dot org. This is the Young
Gazine Brief with Peter Hofland and welcomeback. This is the Angasine Brief.
(20:19):
If you're just joining us In today'sepisode of the Angasine Brief, I'm talking
with doctor David Cocknetti, Doctor Cocknettiis a professor and chair in the Department
of Head and Neck Surgery at ThomasJefferson University Hospital in Philadelphia. Now,
one of the interesting technologies that you'vebeen working on is the racket in medicals
Aluminux platform technology. In our journalsOngazine and ADC Review, a journal of
(20:44):
antibody Druck Conugates, we've written aboutthis technology and the promising scientific and clinical
data from some of the agents basedon this technology platform. In the introduction
of the show today, I brieflygave a short overview of the agents that
are based on this technology. Whereare we right now in the development of
these new agents. Yeah, Soaluminox references something that has been coined photoimmunotherapy,
(21:11):
and I think it's important in describingit talk about the background of photodynamic
therapy, which has been around forseveral decades now, going back to probably
about the nineteen seventies. The conceptof photodynamic therapy is that you can inject
a patient with a light sensitizer,and once they're sensitized, you can shine
(21:33):
a light on the tissue that youwant to destroy, in this case,
the cancer, and then therefore youcan kill the cancer that despite being around
for decades and having been shown tobe efficacious in headnet cancer, it hasn't
really taken off. And some ofthe problems with it are the generalized life
(21:56):
sensitivity that you get with it andjust other challenges to adoption in terms of
cost, etc. Photo immunotherapy differsin a very important way. It conjugates
a monoclonal antibody to that light sensitizer, and theoretically, and what we think
(22:18):
we're seeing in practice, that causestwo major advantages. Number one, it
concentrates the light sensitizer to what you'retrying to kill and treat the tumor,
so better tumor kill. And thentwo, it concentrates it away from the
normal tissue and therefore you don't havethe severe LI sensitivity that's just generalized to
(22:41):
the whole body that was seen withphotodynamic therapy. So those two things together
hypothetically lead to major advantages iluminox.The first monoclonal antibody to be studied is
herbitux, which is one of thedrugs that was approved for treatment. I've
had night cancer going back probably fifteenyears ago, and that's because it's a
(23:06):
monoculon onanibody to the e GFR receptor, which is highly expressed in scream cell
carcinoma. So conceptually, it's areally nice thing that pulls together the biggest
advantages of photodynamic therapy and adds somenice becificity to it to a antibody that's
(23:27):
well expressed in scream and cell carcinomaof that neck. So, if I
understand is correctly, the approach wouldbe best described is something that is similar
to, for example, an antibodytruck cornugate, where you have a tumor
specific antibody that is very specifically targetinga cancer cell. The only difference seems
(23:47):
to me that your payload is inthis case what a soluble photo absorbing dye
and not an anti cancer truck.Right, correct, Right, Because the
dose of the monoclonianibody that conjugated lightsensitizer is not a therapeutic dose. It's
just there to concentrate the light sensitizer. So the payload, the match,
(24:07):
if you will, doesn't get lituntil you shine the light on it.
Now, how do you shine alight on it? How does that work?
In terms of anybody light synthesizer orbecause when the anybody finds its target
cancer cell, it is still limertit does not do anything right. But
when you shine a light on it, it is activated. Now what happens
(24:29):
then, So why don't we talkreal briefly about how we shine the light
on it, because we've talked alot about the complexities of the anatomy of
the headneck. There's two ways todeliver the light. One is if you
think about a flashlight, it's calledthe frontal diffuser. It just shines the
light directly onto the surface of thetumor. It has some penetration up to
(24:51):
about eight millimeters or so, sothat can treat relatively thin superficial tumors or
the superficial aspect of a deeper tObviously, some of these cancers occur under
the skin or under the mucosa andor are thicker than that. And in
that situation, there's catheters that youcan place inside through the tumor, and
(25:15):
then you can deliver it's called thecylindrico suffuser. You can deliver light from
inside the tumor that shines out circumferentiallyfrom the infuser that goes through the catheter.
You can almost think of brakitherapy andradiation where they place catheters and treat
radiation, put radiation seeds in it. We're putting the light inside from inside
(25:37):
the tumor. Now, in simpleterms, what happens when you shine the
light on the antibody light sentesize ofconjugate and bring the light to the tumor.
What happens at that moment? Whatis the effect of decombination? Then,
yeah, the tumor necrosis. Thecells actually pop and they and they
die. And what has always beenamazing to me is that we can visually
(26:03):
see with our naked eye early changeswhile they're even still in the operating room.
So within about a half an houryou can see a dusky color change
to the tumor, and then overthe course of the ensuing days two weeks,
it will truly necros and it's typicallya clean necrosis where it develops an
(26:25):
scar and necrosis away. So thatseems to be a reasonably malt approach.
Now, you were involved in aphase one B and a phase two study
with ASP nineteen twenty nine. Tellme a little bit about to study,
and tell me a little bit aboutsome of the results of that study presented
earlier this year at the annual meetingof the American headed Ex Society in July.
(26:48):
They were presented by a colleague,doctor Anne gillen Water, who presented
the results. She's one of thepeople who's collaborated on this work over the
years. And in this study,the treatment, the luminox treatment was delivered
in combination with pemberlism app and theconcept being that perhaps there can be a
(27:14):
synergistic effect where the luminox can increasethe anergen presentation, if you will,
to the systemic immunotherapy. Right.This is, if I understand this correctly,
a phase one be study. Sohow many patients were enrolled in this
study, and if possible, tellme a little bit more about the conclusions
(27:37):
that you derive from this study.Absolutely, there were a total of nineteen
patients included in the study, andI can tell you that from a safety
standpoint, it was overall well toleratedand there was a objective response rate of
about thirty percent, Which is probablya good time to talk about some of
(27:59):
the challenges we've had in how westudy this, which is that the response
rates are based on resist criteria andif refer back to what we were just
talking about on how the tumor responds, it actually takes some time for the
necrosis to get to the point whereit would be fully appreciated on radiographic imaging.
(28:23):
And what I mean by that,if you were to do ct scans
and follow up on these patients,the necrotic area would look similar in size
and even sometimes in characteristics to thetumor. So by strict RESIST definition,
you have to measure all of that. That's a little bit of a challenge.
(28:47):
I can tell you what we're seeingclinically is that there's very good tumor
kill and tumor response with this asearly as one or two treatments. Add
is indeed very good news. Andmaybe while the number of participating patients may
not seem to be that many,it is good to understand that this is
(29:07):
still a clinical trial. But Iwould say from what you've just described,
the AFL results are very positive.Let's take a break. This is the
Youngest in Brave. If you're justjoining us in today's episode of the Youngest
in Brave, I'm talking with doctorDavis Cooknetti. Doctor Cognetti is a professor
and chair in the Department of Headand Neck Surgery at Thomas Jefferson University Hospital
(29:30):
in Philadelphia. In this episode,we talk about the development of photoimmunotherapy and
head and neck cancer. I'm PeterHoffland and this is the Youngest in Braef.
(29:52):
My name is Jewijehan. I'm thechair of a computational biology department.
As say to Children's Research Hospital thatI feel so excited about seeing the potential
impact not only on the kids treatedas Saint Jude, but across the world.
One of the major advantage we havein Saint Jude is that because of
resources we have, we were ableto utilize the most comprehensive way of profiling
(30:17):
genos through the study. As adata scientist, I feel very passionate about
sharing data. We also want toenable talented scientists to analyze data using the
innovative tools and making new discoveries ontop of what we have made. And
I think this is a great useof the trust we got from our donors
(30:40):
finding cures saving children. Learn moreat Saint Jude dot org. This is
the young Gazine Brief Peter Hoffland andwelcome back. This is the Younger Shim
(31:11):
Brave if you're just joining us intoday's episode of The Youngershim Brave, I'm
talking with doctor David Coocknetti. DoctorCocknetti is professor and chair in the Department
of Head and Neck Surgery at ThomasJefferson University Hospital in Philadelphia. Now,
when you look at ASP nineteen twentynine, there were also other data presented
at this meeting. Tell me alittle bit more about this. So we
(31:34):
have previously reported on a previous phaseone two trial called one on one.
In that trial, it was notcombined with pemberlism ab, and we found
similar response rates that were very encouragingbased on resist. But and we also
found given the treatment population of heavilypreviously treated recurrent disease, unresectable, non
(32:01):
amenable to further chemotherapy radiations. Sothese are really the heaviest hit patients,
if you will. And so wehad respectable survival as well, even though
that wasn't the primary endpoint. Butwhat we did one of the presentations was
to go back to that original populationand look at who's still alive, and
(32:21):
we identified that despite the previous heavytreatment and these patients with overall very poor
prognosis, we had three patients who'vebeen alive for approximately four and up to
five years, So that again hasis very excited about not just the response
(32:45):
rates for this, but the possibilityof getting durable, complete responses and patients
who really have no other options.Some of their studies, not all of
them, our combination therapies. Rightfrom your perspective where you are, how
important are these combination studies, thesecombination strategies. For example, what is
the study which combines ASP nineteen twentynine with prevolution MAPP had to the treatment
(33:09):
of patients diagnosed with a recurrent headand neck cancer. I don't think we
have enough data to answer that question, yet, that's an area of high
interest for further investigation. I cantell you that we've seen it work without
immunotherapy. We've seen it work inpeople who have failed immunotherapy. However,
(33:34):
when I say that we're talking aboutlocal regional disease, right, it would
have to be able to be treatedwith the illuminox so accessible and treated,
which just by that definition limits itsutilization in some of these recurrent patients who
even have distant metastatic disease. SoI think a real promise with the combination
(33:58):
is that we may have an optionfor people who are not only locally recurrent,
but local and distant recurrence who otherwisedon't have very good options. And
the hope would be that the combinationagain sort of priming the immune response with
the energen presentation at the luminox treatmentmight have benefit for even the distant disease.
(34:24):
Of course, that's what we wantto learn from these studies, but
we don't have that data yet.So can you tell me a little bit
more about some of the other studiesas well as plent studies, including a
phase three study with ASP nineteen twentynine. I think the study is called
ASP nineteen twenty nine three or one. Can you tell me a little bit
(34:45):
more about this study and what comesnext, about your expectations for the future
about this technology platform and the agentsthat are based on this. So three
oh one, as you just referredto, is an open three trial.
It's a randomized trial trying to gatherthe randomized data to be able to show
(35:07):
the efficacy of this and hopefully getthis through FDA approval. And then there's
other exciting things in the pipeline.When I described it earlier, I told
you that the illuminox is. It'sa conjugate of monoclonal antibody to licens desires
are it doesn't have to be herbatuxthat is a monoclonal antibody. So there's
(35:28):
all sorts of options for what youcan conjugate to the licensitizer, even antipd
one, etc. So I thinksomebody from Rocketing can talk about their pipeline
better than I can. But thepotential for this, both in terms of
what they can do with the drugas well as other areas in the headneck
(35:51):
including earlier line, I think there'sgreat potential here. I think you're right,
You've saved the best for last inhelping us to understand that the technology
platform also allows the opportunity of creatingan agent with a different antibody, allowing
the development of a pipeline of differentphoto immunotherapy agents. We'll almost at the
end of the program, but inwrapping up, if you look at these
(36:15):
developments developments in the treatment of headand neck cancer and the potential of new
therapeutic approaches, how excited are youabout this? For example, how excited
are you about those new therapeutic approachesincluding photo immunotherapies and the potential it brings
specifically about aluminocs and this technology.I am personally incredibly excited. And I'm
(36:38):
personally excited because, as I justdescribed to you, I've seen with my
own eyes patients who are alive fouror five years who otherwise wouldn't be alive.
And I think we're scratching the surfaceof the potential of this technology because
right now, as we've discussed forthis half hour, we've only really been
(37:00):
able to use it in worst casescenarios. And so if we start using
this and it lives up to thepromise of the showing in these early studies,
it really could be groundbreaking and howwe treat cancer in the future.
Doctor David Cognetti, thank you somuch for joining us today. In the
younger same brief. I'm sure thatat least I hope that this is not
(37:23):
our last conversation, and I hopethat in a near future you can tell
me a little bit more about thesedevelopments you field immunotherapy and the treatment of
head and neck cancers. Again,very exciting news. Thank you so much
for joining us today, Peter.I appreciate that I would be excited to
catch up again in the future.In this episode of the Younger Same Brief,
(37:52):
I spoke with doctor David Coknetti.Doctor Cognetti is a professor and chair
in the Department of Head and NeckSurgery Thomas Jefferson University Hospital in Philadelphia.
Before we Go. As a note, in twenty eighteen, ASP nineteen twenty
nine received a Fast Track designation fromthe US Food and Drug Administration. In
addition, in September twenty twenty,ASP nineteen twenty nine received marketing approval in
(38:16):
Japan from the Ministry of Health,Labor and Welfare. To date, outside
Japan, ASP nineteen twenty nine,Photo Immunotherapy remains an investigational agent. For
related information about photo immunotherapy, theAluminux technology platform ASP nineteen twenty nine,
and clinical trials being conducted, aswell as regulatory decisions, please go to
(38:39):
the website of Recuton Medical that isrecutandashmat dot com forwardsless US. For more
information about Heaton neck cancer and aboutstudies presented in this program, please go
to our online journal oncozine at oncozinedot com that is oncoziene dot com for
(38:59):
US here at Brief, we wantto thank you our listeners, sponsors,
and advertisers for your ongoing support.Your support makes it possible that you can
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and streaming media including iTunes, Spotify, Audible, Stitcher, SoundCloud, and
(39:22):
nearly anywhere you can find a podcast. For more information about supporting the Ogasine
Brief, visit our website at Ongazineat ongazine dot com. If you're living
in the United States and want toreceive our newsletter, text the word cancer
to six six eight six six,that is six six eight six six and
(39:42):
we will make sure that you'll receiveour newsletter, which includes an overview of
the latest news in oncology and hematology. Thank you all, and thank you
for listening and join us again forour next episode. I'm Peter Hofland and
this is the Youngest in Brief.The Ongazine Brief is a global medical educational
(40:09):
service from the publishers of Oncazine andADC Review, the Journal of Antibody Drug
Conjugates. Support for the on GazineBrief comes from our commercial underwriters and advertisers
and the listeners to this station.For more information about advertising, underwriting,
and sponsoring options, visit Onkazine atwww dot onkazine dot com, Forward Slash
(40:30):
podcasts. The Oncazine Brief contains healthand medicine related information and is provided for
educational and entertainment purposes only. Thecontent in this program is not intended as
a substitute for professional medical or healthadvice, and does not replace your doctor's
advice and guidance. Your doctor isthe best person to answer questions about your
personal health. If you hear somethingin this program that doesn't agree with what
(40:52):
your doctor has told you, askhim or her about it.
This is The Youngazine Brief with PeterHoffland. Welcome to a new episode of
The Angasine Brief. I'm Peter Hofland, and in this episode of the program,
I'll be talking with doctor David Coocknetti, a professor and chair in the
Department of headen Neck Surgery at ThomasJefferson University Hospital in Philadelphia. In this
(00:34):
episode, we talk about head andneck cancer and a novel treatment approach called
photo immunotherapy. According to the AmericanCancer Society, head and neck cancer accounts
for approximately four percent of all cancersin the United States and in twenty twenty
three, this translates to approximately sixtyseven thousand people who will be diagnosed with
(00:54):
head and neck cancer and about fifteenthousand patients who are expected to die of
the disease. Today, many cancersof the head and neck can be cured,
especially if they are found early andWhile eliminating the cancer is the primary
goal of treatment, preserving the functionof the nearby nerves, organs, and
tissue is also very important and iswhere photoimmunotherapy may start a player role.
(01:19):
Photoimmunotherapy is a recently developed hybrid cancertherapy to treat cancers by linking specific antibodies
with photosynthesizers to form photoimmunoconjugates. Butlet's go back to the beginning. Surgery,
radiation, and chemotherapy have dominated thetreatment of oncology. These therapies aim
to eradicate cancer cells, but unfortunatelyoften do that at the expense of normal
(01:42):
or healthy cells. In turn,this can lead to severe and sometimes lethal
side effects. Overall, the successof cancer therapy, including surgery, radiation,
and chemotherapy are measured by what wecall a therapeutic index. This therapeutic
index compare the potential benefits of treatmentto the potential risk associated with these treatment.
(02:05):
Unfortunately, the unintended off target sideeffects of these therapies can have profound
effects on the health related quality oflife of patients. For example, boat
radiation and chemotherapy sometimes preferentially kill lymphocytesmuch earlier than cancer cells. This happens
because of the increased radiation sensitivity andhigh proliferation rate of lymphocytes, potentially leading
(02:28):
to those limiting toxicities for some treatmentregiments. To find the solution, researchers
have developed new therapeutic strategies, andwhile these therapies have created new and exciting
directions for the treatment of cancer.They remain limitations to these novel approaches.
Now, in theory, the perfectcancer therapy would bote directly destroy cancer cells
(02:50):
to minimize residual cancer cells, aswell as activate the local host immune response
to wipe out remaining cancer cells,and such a therapy would be highly selective
for cancer cells but have minimal orno off target effects in a tumor micro
environment, and that is where photoimmunotherapycomes in. Photoimmunotherapy is designed to selectrically
(03:14):
destroy cancer cells. This therapy indusesdirect cancer killing via immunogenic cell death,
thus activating the anti cancer immune systemlocally in the tumor micro environment. The
specificity of this approach comes from theantibody that is designed to target an expressed
antigen on a tumor surface and isconjugated to a photoactivating chemical. The safety
(03:36):
of photoimmunotherapy is based on the factthat the antibody photoactivating chemical conjugate predominantly binds
to specifically targeted cancer cells and thatit is only activated in areas exposed to
near infrared light at a specific activatingwavelength. By choosing tumor specific antigens.
This therapy specifically destroys cancer cells,while not or only minimum harming any adjacent's
(04:00):
normal or healthy cells, particularly tumorinfiltrating immune T cells or blood vessels.
Furthermore, the photo activating chemical isa water soluble photo absorbing dye with outside
the toxic properties of its own.Clinical studies have shown that this combination can
enhance the immune response and as aresult, have a good effect on the
(04:23):
treatment of residual tumor and metastatic cancer. The first human study of a photo
immunotherapy was with ASP nineteen twenty nine, which is being developed by Racket and
Medical and is used for the treatmentof inoperable head and neck cancer. ASP
nineteen twenty nine is a conjugate ofstoximab, an anti eedfr antibody plus the
(04:44):
photo absorber or photo activating chemical calledR seven hundred. I'm Peter Hoffland and
this is the Youngosine Brief. TheYoungesine Brief is developed in collaboration with our
online journal on Coosine, where youcan find additional information in the latest news
about cancer, cancer diagnosis and treatment, and cancer prevention. For more information
on how to support this program,visit our website at oncozine, and if
(05:09):
you're living in the United States andwant to receive our newsletter, text the
word cancer to six six eight sixsix and we will make sure that you'll
receive our newsletter, which includes anoverview of the latest news in oncology and
hematology. This is the Ongazine Brief. For the latest news about cancer and
(05:34):
cancer treatment, visit our online journalOncazine at www dot kazine dot com.
On the phone with me is doctorDavid Cocknetti. Doctor Cocknetti is a professor
and chair in the Department of Headand Neck Surgery at Thomas Jefferson University Hospital
in Philadelphia. Doctor Cocknetti, welcometo the Angasine Brief. Now, before
(05:56):
we come to talk about photo immunotherapyand some very interesting data and results presented
at this year's annual meeting of theAmerican Head and Next Society, tell me
a little bit more about yourself andhow you got here. So I'm David
Agnetti, as you've already recognized,I'm a head neck cancer surgeon. I'm
based out of Thomas Jefferson University inPhiladelphia, and I got interested in treating
(06:19):
patients with headnet cancer. Going backto my training years in medical school at
the University of Pittsburgh, I wasexposed to doctor Jean Myers and Jonas Johnson
and others that really introduced me tothe field. And when I did my
residency training at Jefferson, which iswhere I ended up long term, it
(06:41):
just solidified that these were the patientsthat I wanted to help care for throughout
my career. Now, head andneck cancers are very difficult to treat.
Can you give me a little bitbackground how these cancers are treated today?
And in additionally, why is thisdisease so difficult to treat? That's an
excellent question. Headnet cancer is difficultto treat for a couple of reasons.
(07:04):
Number one is the anatomy that itimpacts. If you think about it,
your face and your head neck.That's your presentation of the world. So
not only is it your appearance,but it's also the area of many of
our most vital functions communicating, breathing, eating, So headnet cancer or the
(07:26):
treatments to cure it or try tocure it, have impact on all of
those vital functions and a person's presentationof the world, So it can be
very devastating for the patient. Interestingly, headnet cancer has evolved over the last
twenty years. I just gave youmy background of what made me interested in
it. When I was first startingoff in medical school, the only or
(07:49):
the major causes of headnet cancer weresmoking, tobacco or any use of tobacco
and alcohol. And now fast forward, a major cause and the biggest driver
of oral forngeal cancer or throw canceris HPV human papalona virus. And so
(08:11):
we've seen a shift in the typesof patients we're seeing and at the same
time, we've had major shifts intreatment options for these patients. So it's
as devastating as it can be asa disease, it's still a very exciting
time to be in the business ofcaring for this disease. Let's take a
break. This is the Younger ShameBraef. If you're just joining us.
(08:35):
In today's episode of The Younger ShameBraef, I'm talking with doctor Davis Cocknetti.
Doctor Cocknetti is a professor and chairin the Department of Head and Neck
Surgery at Thomas Jefferson University Hospital inPhiladelphia. In this episode, we talk
about the development of photoimmunotherapy and headand neck cancer. I'm Peter Hoffland and
this is the younger shim Braef.Each day, researchers make new discoveries that
(09:07):
bring us closer to the moment whenall cancer patients can become survivors. Some
days they take small steps, others, huge discoveries lead to giant leaps forward.
This progress, both small steps andgiant leaps, happens with the health
of clinical trials. Clinical trials area fundamental path to progress and the brightest
(09:28):
torch researchers have to light their waytowards better treatments, and if you've been
diagnosed with cancer, they may beyour brightest ray of hope. Clinical trials
introduce new hope in addition to thecurrent standard of care by allowing researchers to
provide participants access to cutting edge andpotentially life saving treatments. So if you're
(09:48):
interested in exploring new treatment options whilehelping to light the path for other patients,
clinical trials may be the best choicefor you. Speak with your doctor
and visit stand Up to cancer dotorg slash clinical trials to learn more about
clinical trials. Together, we canstand up for all of us This is
(10:13):
the Young Gazine Brief with Peter Hofflandand welcome back. This is the Younger
Him Brief. If you're just joiningus in today's episode of The Angus Him
Brave. I'm talking with doctor DavidCoocknetti. Doctor Cocknetti is professor and chair
in the Department of Head and NeckSurgery at Thomas Jefferson University Hospital in Philadelphia.
(10:39):
So, during the recent annual meetingfrom the American Society of Clinical Oncology
or ASCO, they were presentations talkingabout these transitions from smoking related head and
neck cancer. If I recall correctlyto HPV, those two forms of cancer,
how different are they? For example, when you have a patient that
is diagnosed with head and neck cancerthat is caused by smoking, or you
(11:01):
have a patient has been diagnosed withheadoneck cancer links to HPV associated with oral
sex, how different are those formsof cancer. They're very different, both
the cancer itself, the prognosis forthe cancer self is different, and the
people who get them, the riskfactors that lead to it. So the
traditional headneck cancer caused by smoking anddrinking is generally an older generally occur as
(11:28):
an older gentleman who have a lotof other comorbidities caused by smoking, So
if they were to survive their cancer, oftentimes they don't have a very good
overall survival because they're the ones whoare getting heart attacks and strokes and other
things that are also caused by smoking, lung cancer, etc. And on
(11:50):
top of that, of the twocancer types, it's a much harder one
to cure the ones that are notrelated to HPV. Now, the ones
that are related to HPV that happensnow in younger people who have never smoked.
So when it first came on thescene was a little confusing, why
are these people getting cancer? Nowwe have a very clear understanding of why
(12:13):
they're getting the cancer, but it'sin people who don't have the other commorabilities
caused by smoking. So if youtake instead of a sixty five year old
person, you have a forty fiveyear old person, And instead of somebody
who's at risk of heart attack,lung cancer, and stroke, you have
somebody who is a very healthy person. And now you add on that they
(12:35):
are more likely to be cured.Well, you have to count now that
they're going to be around for decadesinstead of the other type where they generally
wouldn't live for decades. So howwe treat these patients keeping in mind their
functional outcomes over the years is veryimportant. And if you look at the
available treatment options for a patient thatis diagnosed with head the neck can are
(13:00):
linked to smoking or head neck cancerlinked to HBV and oral six in i
a case, what is the currentstandard therapy and the best treatment options for
those cancers? Cancer? In general? The treatment options are any combination of
surgery, radiation and chemotherapy. Arethose are the very traditional one And what's
(13:22):
interesting we say headnet cancer, butheadnet cancer is actually a collection a bunch
of smaller subsite cancers. And whatI mean by that, although we bucket
them into headnet cancer, and althoughthey're almost always scream as cell cancer which
is the surface cell, the tonguecancer or oral tongue cancer, the front
end of the tongue behaves very differentlythan base of tongue cancer. The back
(13:46):
of the tongue behaves very differently thanlarynx cancer. The voice box behaves differently
than hypofarings cancers, so and nasopharingx cancer. They're all individually have different
treatment algorithms and agnoses. In someof them, for example, the oral
cavity surgery is the preferred treatment,and some of them, for example,
the nasal farings, radiation and chemotherapies of preferred treatment. So it's different
(14:11):
depending on the exact subsite, whichis only centimeters away from each other,
and based on what you said earlierin this program, surgery may be difficult
because it is such a complex,anatomical and very congested area, right,
So tell me a little bit moreabout this in case surgery is needed.
It's very complex and difficult, right. It's anatomically complex and it's functionally important.
(14:35):
So yes, those two things addup for making surgery difficult, and
unfortunately, there's been advances on howwe do surgery with a higher prioritization in
modern day surgery compared to the paston making sure we account and preserve function.
Now, when you look at thefield today and you look at the
(14:56):
options for treatment, the kind ofpatient that you're dealing with, what would
you say are some of the unmetmedical needs that patients are facing in terms
of the availability of treatment options andlimitations to treatment for patients you may not
be able to treat. What aresome of the issues that you're encountering you
practice today, so unmet needs.There are still many of these patients that
(15:18):
are not being cured. So numberone priority is to improve the cure rate.
And then we've touched on a numberof times here how destructive our current
treatments can be to the function ofthe patient. So if you're doing surgery,
you're cutting out tissue, and soeven if it replaces the non functional,
(15:41):
radiation has long term devastation on thenormal tissue, causes fibrosis, it
stiffening of the tissue, it causesdry mouth and zerostomia, and really ruins
the normal tissue. And chemotherapy canhave acute toxic effects and make the effects
(16:02):
of radiation that the side effects evenworse. So wrapped up in all of
that, there's plenty of room forimprovement on both curing these patients and curing
them with their highest quality of lifebecause again, the location and the impact
of this cancer and the treatments ofsignificant manifestations on quality of life. Now
(16:26):
you've been working and treating patients forquite some time. If you look back
at studies presented at different medical andclinical meetings from the American Society of Clinical
Oncology, the American Association of CancerResearch and the American Head and Neck Society,
and maybe some other meetings. Thereis still the question that are here
often are there any new treatment optionsfor head and neck cancer coming out?
(16:48):
Are there new things available? Incontrast, for example, if you look
at breast cancer, treatment options forhead and neck cancer seems to be very
slow incoming. Later in our program, we'll be talking a little bit about
photo immunotherapy and the results of ongoingstudies you've been involved with. Some of
these developments have been in development fora long time. But tell me,
(17:11):
other than the complexities of the diseaseitself, which we talked about, are
there other reasons why it is sodifficult to develop new treatment options or why
is the field moving so slowly?That's a great question. I think you
could look at the field almost dichotomously, and what I mean by that is
in recent years, it seems likethings are really speeding up in new discovery,
(17:33):
new options ofmunotherapy, and what we'reseeing across cancer care in general.
But you're right, if you takea broader picture view and step back,
it's been slow advance, very slowmovement of the needle in terms of overall
survival for these patients. With thebiggest impact on survival and headnet cancer is
(17:55):
probably the virus itself, human papulomavirus. By more of the cancer being
related to human papuloma virus, thatin turn has improved survivorability. Not necessarily
that our treatments got better. Wewere just treating a better prognosis disease.
So you're right. So part ofit is that's what it takes to develop
cancer care treatments. Part of itis when new exciting things come on,
(18:21):
we do have to carefully study themin a way that doesn't put at risks
the patients and the gains that havealready been made. And so you know,
clinical trials of the appropriate design andpower take time, They take years
to report out. Let's take abreak. This is the Young Mashine Brief.
(18:41):
If you're just joining us in today'sepisode of the Young Mashine Brief,
I'm talking about doctor David Cooknetti.I'm Peter Hoffland, and this is the
Young Mashine Brief. Odds are you'venever heard that word before, but for
(19:03):
the forty people diagnosed with sarcoma everyday, it is a life changing word,
life changing and devastating because sarcoma iscancer. Sarcoma is a cancer of
bone and soft tissue, more prevalentin children than in adults. More than
six thousand people lose their lives tosarcoma each year. Treatment options for sarcoma
are limited, and new therapies aredesperately needed. More research and increased awareness
(19:27):
is necessary to find a cure fora cancer that you probably didn't even know
existed until now. Through awareness,advocacy, and research, the Sarcoma Foundation
of America is determined to help thoseaffected by this forgotten cancer. To bring
hope to the children and adults whoselives are forever changed by a word they
had never heard before. Please helpus in the fight to find the cure
(19:49):
for sarcoma. For more information onsarcoma and the work of the Sarcoma Foundation
of America, please go to CureSarcoma dot org. This is the Young
Gazine Brief with Peter Hofland and welcomeback. This is the Angasine Brief.
(20:19):
If you're just joining us In today'sepisode of the Angasine Brief, I'm talking
with doctor David Cocknetti, Doctor Cocknettiis a professor and chair in the Department
of Head and Neck Surgery at ThomasJefferson University Hospital in Philadelphia. Now,
one of the interesting technologies that you'vebeen working on is the racket in medicals
Aluminux platform technology. In our journalsOngazine and ADC Review, a journal of
(20:44):
antibody Druck Conugates, we've written aboutthis technology and the promising scientific and clinical
data from some of the agents basedon this technology platform. In the introduction
of the show today, I brieflygave a short overview of the agents that
are based on this technology. Whereare we right now in the development of
these new agents. Yeah, Soaluminox references something that has been coined photoimmunotherapy,
(21:11):
and I think it's important in describingit talk about the background of photodynamic
therapy, which has been around forseveral decades now, going back to probably
about the nineteen seventies. The conceptof photodynamic therapy is that you can inject
a patient with a light sensitizer,and once they're sensitized, you can shine
(21:33):
a light on the tissue that youwant to destroy, in this case,
the cancer, and then therefore youcan kill the cancer that despite being around
for decades and having been shown tobe efficacious in headnet cancer, it hasn't
really taken off. And some ofthe problems with it are the generalized life
(21:56):
sensitivity that you get with it andjust other challenges to adoption in terms of
cost, etc. Photo immunotherapy differsin a very important way. It conjugates
a monoclonal antibody to that light sensitizer, and theoretically, and what we think
(22:18):
we're seeing in practice, that causestwo major advantages. Number one, it
concentrates the light sensitizer to what you'retrying to kill and treat the tumor,
so better tumor kill. And thentwo, it concentrates it away from the
normal tissue and therefore you don't havethe severe LI sensitivity that's just generalized to
(22:41):
the whole body that was seen withphotodynamic therapy. So those two things together
hypothetically lead to major advantages iluminox.The first monoclonal antibody to be studied is
herbitux, which is one of thedrugs that was approved for treatment. I've
had night cancer going back probably fifteenyears ago, and that's because it's a
(23:06):
monoculon onanibody to the e GFR receptor, which is highly expressed in scream cell
carcinoma. So conceptually, it's areally nice thing that pulls together the biggest
advantages of photodynamic therapy and adds somenice becificity to it to a antibody that's
(23:27):
well expressed in scream and cell carcinomaof that neck. So, if I
understand is correctly, the approach wouldbe best described is something that is similar
to, for example, an antibodytruck cornugate, where you have a tumor
specific antibody that is very specifically targetinga cancer cell. The only difference seems
(23:47):
to me that your payload is inthis case what a soluble photo absorbing dye
and not an anti cancer truck.Right, correct, Right, Because the
dose of the monoclonianibody that conjugated lightsensitizer is not a therapeutic dose. It's
just there to concentrate the light sensitizer. So the payload, the match,
(24:07):
if you will, doesn't get lituntil you shine the light on it.
Now, how do you shine alight on it? How does that work?
In terms of anybody light synthesizer orbecause when the anybody finds its target
cancer cell, it is still limertit does not do anything right. But
when you shine a light on it, it is activated. Now what happens
(24:29):
then, So why don't we talkreal briefly about how we shine the light
on it, because we've talked alot about the complexities of the anatomy of
the headneck. There's two ways todeliver the light. One is if you
think about a flashlight, it's calledthe frontal diffuser. It just shines the
light directly onto the surface of thetumor. It has some penetration up to
(24:51):
about eight millimeters or so, sothat can treat relatively thin superficial tumors or
the superficial aspect of a deeper tObviously, some of these cancers occur under
the skin or under the mucosa andor are thicker than that. And in
that situation, there's catheters that youcan place inside through the tumor, and
(25:15):
then you can deliver it's called thecylindrico suffuser. You can deliver light from
inside the tumor that shines out circumferentiallyfrom the infuser that goes through the catheter.
You can almost think of brakitherapy andradiation where they place catheters and treat
radiation, put radiation seeds in it. We're putting the light inside from inside
(25:37):
the tumor. Now, in simpleterms, what happens when you shine the
light on the antibody light sentesize ofconjugate and bring the light to the tumor.
What happens at that moment? Whatis the effect of decombination? Then,
yeah, the tumor necrosis. Thecells actually pop and they and they
die. And what has always beenamazing to me is that we can visually
(26:03):
see with our naked eye early changeswhile they're even still in the operating room.
So within about a half an houryou can see a dusky color change
to the tumor, and then overthe course of the ensuing days two weeks,
it will truly necros and it's typicallya clean necrosis where it develops an
(26:25):
scar and necrosis away. So thatseems to be a reasonably malt approach.
Now, you were involved in aphase one B and a phase two study
with ASP nineteen twenty nine. Tellme a little bit about to study,
and tell me a little bit aboutsome of the results of that study presented
earlier this year at the annual meetingof the American headed Ex Society in July.
(26:48):
They were presented by a colleague,doctor Anne gillen Water, who presented
the results. She's one of thepeople who's collaborated on this work over the
years. And in this study,the treatment, the luminox treatment was delivered
in combination with pemberlism app and theconcept being that perhaps there can be a
(27:14):
synergistic effect where the luminox can increasethe anergen presentation, if you will,
to the systemic immunotherapy. Right.This is, if I understand this correctly,
a phase one be study. Sohow many patients were enrolled in this
study, and if possible, tellme a little bit more about the conclusions
(27:37):
that you derive from this study.Absolutely, there were a total of nineteen
patients included in the study, andI can tell you that from a safety
standpoint, it was overall well toleratedand there was a objective response rate of
about thirty percent, Which is probablya good time to talk about some of
(27:59):
the challenges we've had in how westudy this, which is that the response
rates are based on resist criteria andif refer back to what we were just
talking about on how the tumor responds, it actually takes some time for the
necrosis to get to the point whereit would be fully appreciated on radiographic imaging.
(28:23):
And what I mean by that,if you were to do ct scans
and follow up on these patients,the necrotic area would look similar in size
and even sometimes in characteristics to thetumor. So by strict RESIST definition,
you have to measure all of that. That's a little bit of a challenge.
(28:47):
I can tell you what we're seeingclinically is that there's very good tumor
kill and tumor response with this asearly as one or two treatments. Add
is indeed very good news. Andmaybe while the number of participating patients may
not seem to be that many,it is good to understand that this is
(29:07):
still a clinical trial. But Iwould say from what you've just described,
the AFL results are very positive.Let's take a break. This is the
Youngest in Brave. If you're justjoining us in today's episode of the Youngest
in Brave, I'm talking with doctorDavis Cooknetti. Doctor Cognetti is a professor
and chair in the Department of Headand Neck Surgery at Thomas Jefferson University Hospital
(29:30):
in Philadelphia. In this episode,we talk about the development of photoimmunotherapy and
head and neck cancer. I'm PeterHoffland and this is the Youngest in Braef.
(29:52):
My name is Jewijehan. I'm thechair of a computational biology department.
As say to Children's Research Hospital thatI feel so excited about seeing the potential
impact not only on the kids treatedas Saint Jude, but across the world.
One of the major advantage we havein Saint Jude is that because of
resources we have, we were ableto utilize the most comprehensive way of profiling
(30:17):
genos through the study. As adata scientist, I feel very passionate about
sharing data. We also want toenable talented scientists to analyze data using the
innovative tools and making new discoveries ontop of what we have made. And
I think this is a great useof the trust we got from our donors
(30:40):
finding cures saving children. Learn moreat Saint Jude dot org. This is
the young Gazine Brief Peter Hoffland andwelcome back. This is the Younger Shim
(31:11):
Brave if you're just joining us intoday's episode of The Youngershim Brave, I'm
talking with doctor David Coocknetti. DoctorCocknetti is professor and chair in the Department
of Head and Neck Surgery at ThomasJefferson University Hospital in Philadelphia. Now,
when you look at ASP nineteen twentynine, there were also other data presented
at this meeting. Tell me alittle bit more about this. So we
(31:34):
have previously reported on a previous phaseone two trial called one on one.
In that trial, it was notcombined with pemberlism ab, and we found
similar response rates that were very encouragingbased on resist. But and we also
found given the treatment population of heavilypreviously treated recurrent disease, unresectable, non
(32:01):
amenable to further chemotherapy radiations. Sothese are really the heaviest hit patients,
if you will. And so wehad respectable survival as well, even though
that wasn't the primary endpoint. Butwhat we did one of the presentations was
to go back to that original populationand look at who's still alive, and
(32:21):
we identified that despite the previous heavytreatment and these patients with overall very poor
prognosis, we had three patients who'vebeen alive for approximately four and up to
five years, So that again hasis very excited about not just the response
(32:45):
rates for this, but the possibilityof getting durable, complete responses and patients
who really have no other options.Some of their studies, not all of
them, our combination therapies. Rightfrom your perspective where you are, how
important are these combination studies, thesecombination strategies. For example, what is
the study which combines ASP nineteen twentynine with prevolution MAPP had to the treatment
(33:09):
of patients diagnosed with a recurrent headand neck cancer. I don't think we
have enough data to answer that question, yet, that's an area of high
interest for further investigation. I cantell you that we've seen it work without
immunotherapy. We've seen it work inpeople who have failed immunotherapy. However,
(33:34):
when I say that we're talking aboutlocal regional disease, right, it would
have to be able to be treatedwith the illuminox so accessible and treated,
which just by that definition limits itsutilization in some of these recurrent patients who
even have distant metastatic disease. SoI think a real promise with the combination
(33:58):
is that we may have an optionfor people who are not only locally recurrent,
but local and distant recurrence who otherwisedon't have very good options. And
the hope would be that the combinationagain sort of priming the immune response with
the energen presentation at the luminox treatmentmight have benefit for even the distant disease.
(34:24):
Of course, that's what we wantto learn from these studies, but
we don't have that data yet.So can you tell me a little bit
more about some of the other studiesas well as plent studies, including a
phase three study with ASP nineteen twentynine. I think the study is called
ASP nineteen twenty nine three or one. Can you tell me a little bit
(34:45):
more about this study and what comesnext, about your expectations for the future
about this technology platform and the agentsthat are based on this. So three
oh one, as you just referredto, is an open three trial.
It's a randomized trial trying to gatherthe randomized data to be able to show
(35:07):
the efficacy of this and hopefully getthis through FDA approval. And then there's
other exciting things in the pipeline.When I described it earlier, I told
you that the illuminox is. It'sa conjugate of monoclonal antibody to licens desires
are it doesn't have to be herbatuxthat is a monoclonal antibody. So there's
(35:28):
all sorts of options for what youcan conjugate to the licensitizer, even antipd
one, etc. So I thinksomebody from Rocketing can talk about their pipeline
better than I can. But thepotential for this, both in terms of
what they can do with the drugas well as other areas in the headneck
(35:51):
including earlier line, I think there'sgreat potential here. I think you're right,
You've saved the best for last inhelping us to understand that the technology
platform also allows the opportunity of creatingan agent with a different antibody, allowing
the development of a pipeline of differentphoto immunotherapy agents. We'll almost at the
end of the program, but inwrapping up, if you look at these
(36:15):
developments developments in the treatment of headand neck cancer and the potential of new
therapeutic approaches, how excited are youabout this? For example, how excited
are you about those new therapeutic approachesincluding photo immunotherapies and the potential it brings
specifically about aluminocs and this technology.I am personally incredibly excited. And I'm
(36:38):
personally excited because, as I justdescribed to you, I've seen with my
own eyes patients who are alive fouror five years who otherwise wouldn't be alive.
And I think we're scratching the surfaceof the potential of this technology because
right now, as we've discussed forthis half hour, we've only really been
(37:00):
able to use it in worst casescenarios. And so if we start using
this and it lives up to thepromise of the showing in these early studies,
it really could be groundbreaking and howwe treat cancer in the future.
Doctor David Cognetti, thank you somuch for joining us today. In the
younger same brief. I'm sure thatat least I hope that this is not
(37:23):
our last conversation, and I hopethat in a near future you can tell
me a little bit more about thesedevelopments you field immunotherapy and the treatment of
head and neck cancers. Again,very exciting news. Thank you so much
for joining us today, Peter.I appreciate that I would be excited to
catch up again in the future.In this episode of the Younger Same Brief,
(37:52):
I spoke with doctor David Coknetti.Doctor Cognetti is a professor and chair
in the Department of Head and NeckSurgery Thomas Jefferson University Hospital in Philadelphia.
Before we Go. As a note, in twenty eighteen, ASP nineteen twenty
nine received a Fast Track designation fromthe US Food and Drug Administration. In
addition, in September twenty twenty,ASP nineteen twenty nine received marketing approval in
(38:16):
Japan from the Ministry of Health,Labor and Welfare. To date, outside
Japan, ASP nineteen twenty nine,Photo Immunotherapy remains an investigational agent. For
related information about photo immunotherapy, theAluminux technology platform ASP nineteen twenty nine,
and clinical trials being conducted, aswell as regulatory decisions, please go to
(38:39):
the website of Recuton Medical that isrecutandashmat dot com forwardsless US. For more
information about Heaton neck cancer and aboutstudies presented in this program, please go
to our online journal oncozine at oncozinedot com that is oncoziene dot com for
(38:59):
US here at Brief, we wantto thank you our listeners, sponsors,
and advertisers for your ongoing support.Your support makes it possible that you can
hear this program via PRX Public RadioChange and in the United Kingdom and mainland
Europe via UK Health Radio. Andyou can also download our program via podcast
and streaming media including iTunes, Spotify, Audible, Stitcher, SoundCloud, and
(39:22):
nearly anywhere you can find a podcast. For more information about supporting the Ogasine
Brief, visit our website at Ongazineat ongazine dot com. If you're living
in the United States and want toreceive our newsletter, text the word cancer
to six six eight six six,that is six six eight six six and
(39:42):
we will make sure that you'll receiveour newsletter, which includes an overview of
the latest news in oncology and hematology. Thank you all, and thank you
for listening and join us again forour next episode. I'm Peter Hofland and
this is the Youngest in Brief.The Ongazine Brief is a global medical educational
(40:09):
service from the publishers of Oncazine andADC Review, the Journal of Antibody Drug
Conjugates. Support for the on GazineBrief comes from our commercial underwriters and advertisers
and the listeners to this station.For more information about advertising, underwriting,
and sponsoring options, visit Onkazine atwww dot onkazine dot com, Forward Slash
(40:30):
podcasts. The Oncazine Brief contains healthand medicine related information and is provided for
educational and entertainment purposes only. Thecontent in this program is not intended as
a substitute for professional medical or healthadvice, and does not replace your doctor's
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personal health. If you hear somethingin this program that doesn't agree with what
(40:52):
your doctor has told you, askhim or her about it.
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