- This is Laura Dedo with the Becker's Healthcare Podcast.
I'm thrilled today to be joined by Dr.
Guru Sode, who's the medical director of Janitor
Oncology in the Phase one Cancer Research Unit at Advent
Health Cancer Institute.
Dr. Sode, it's a pleasure to have you on the podcast today.
- Thank you for having me on.
- Now, I'm looking forward to our discussion.
I know we're gonna dive deep into some of the
clinical research that you're doing
and really exciting work around, uh,
a new bladder cancer therapy
and vaccine that is really, you know,
representing the forefront of, uh, precision oncology.
But before we dive into that discussion,
can you tell us a little bit more about, uh,
yourself and your background?
- Yeah, thank you for the opportunity.
So my background is I'm a medical oncologist
and focused on clinical trials.
I have been focused on, um, continuing to urinary cancers,
which includes, uh, bladder, prostate, and kidney cancer,
and other, some other urologic system cancers.
I have primarily been focused on bladder cancer,
but at Advent Health,
I'm also leading the phase one clinical trial program,
which, uh, essentially investigate new drugs coming from
the lab into the clinic to, um, look at the safety
and the feasibility of, uh, taking the, some
of these drugs further to treat patients
with advanced cancers.
- Well, it's fascinating to hear,
and you know, really such a important,
in rewarding place to be.
Now, I know you recently had a trial that you were part
of get FDA approval.
Can you tell us about that trial and treatment?
- Yes. I was fortunate to be, uh, one of the co-leaders
of a phase three trial called the Checkmate 9 0 1 trial.
This is a phase three trial in which had several components.
The component that, uh, was, uh, recently in the news
and led to the approval of a new drug, um,
is a component that compared, uh, first line chemotherapy
with cisplatin and gemcitabine in advanced
urothelial carcinoma, and that's mostly bladder cancer.
Um, although there are patients also
with upper urinary tract carcinoma, uh,
which had metastasized.
So in these patients, um,
who are cisplatin eligible fit enough
to receive the cisplatin based chemotherapy,
the trial compared cisplatin plus gemcitabine, which is the
standard, which was a standard back then.
And this was compared with cisplatin gemcitabine plus
nivolumab a PD one inhibitor.
So essentially, uh, this combination with nivolumab,
the PD one inhibitor, immunotherapy drug,
which essentially turns out on the, to fight them
and, uh, attack these cancer cells, did lead
to an improvement in survival.
And this led to us FDA approval for patients, um,
who were receiving cisplatin
and gemcitabine chemotherapy as first line therapy
for advanced urothelial carcinoma.
The key highlight of this trial was
that there was a 22% complete remission rate, uh,
which is the total resolution of all
of the visible disease on the scans.
And the patients who had a complete remission had a very
long duration of response within median duration
of a little over three years.
And so this is, um, um, a promising, uh, finding in, uh,
this group of patients.
Uh, and this, uh, this data really led
to the US FDA approving this combination cisplatin
gemcitabine plus nivolumab in patients who were, uh,
eligible for cisplatin
and had advanced urothelial carcinoma.
- Well, that's fascinating to hear
and really interesting to, um, know that, you know,
this type of work is out there and can be so successful.
Now, there's also a new phase two trial at Advent Health
Cancer Institute located in central Florida
that just opened in April for bladder cancer patients.
What makes this trial unique
and what does this mean for the customized medicine?
- Right. We are especially excited about this, uh,
new randomized phase two trials that just opened, uh,
actually globally and oversight in, uh, Florida.
The Advent Health Cancer program is actually the only site,
uh, open in Florida and, uh, one
of the first sites globally,
and the first site in the US to open, actually.
So this is the phase two trial,
which looks at a different stage of the disease.
This is patients who have urothelial carcinoma, um,
in the urinary tract that's been removed surgically,
but they still have a high risk of recurrence.
Uh, so there might be basically microscopic
disease somewhere that's not visible yet that might grow
with time and, um, then become known as metastatic disease.
So in these patients, um, what we know is, um, postoperative
or adjuvant nivolumab, uh,
PD one inhibitor immunotherapy drug is approved.
But what is also known is
that very recently the randomized phase three trial called
the ambassador trial, uh, showed
that there was an improvement also
with adjuvant pembrolizumab.
Uh, and so pembrolizumab is, um, awaiting us FDA reviews.
But what this study is doing here,
this is called the inter path 0 0 5 trial.
Um, this is a randomized phase two trial, which tries
to improve upon the efficacy of pembrolizumab.
Uh, so basically patients
with high risk urothelial carcinoma who under,
who have undergone surgery, are randomized to pembrolizumab,
combined with, uh, placebo versus pembrolizumab, combined
with the V nine 40, uh, which is the experimental new agent.
And I will explain that in a second,
but basically what I want to explain is in this trial, uh,
nobody is getting only placebo, so all
of the patients get pembrolizumab,
and one half of the patients, uh,
is also receiving the V nine 40,
which is given intramuscularly every three
weeks for nine cycles.
So the V nine 40 is an extremely exciting
immunotherapy agent.
Um, what it is, is it codes for the,
um, neoantigens found specifically in the cancer cell.
So neoantigen are new proteins
found only in the cancer cells
because of the mutations found only in the cancer cells.
So essentially, when you have, um,
a molecule like the V nine 40, which codes
for these new proteins
or new antigen using the RNA, the corresponding RNA
for the these proteins, remember the DNA codes
for R-N-A-R-N-A codes for protein.
So what, um, um, uh, the sponsoring company has done here,
uh, this is Merck in collaboration with Moderna,
is made this mRNA immunotherapeutic, which codes for this,
uh, up to 34 neoantigens found only in the cancer cell.
And this product is, uh,
injected into the patient's intramuscularly every three
weeks, uh, uh, up to nine times.
So this is an extremely specific highly, uh, precise, uh,
precision immunotherapy, um, in my judgment, uh,
which has been looking very promising
so far in a smaller phase two trial, uh,
in melanoma a different cancer,
there was a significant improvement in the outcomes.
And this has led to a phase three trial in melanoma.
And really, so this kind of an approach, uh,
precision immunotherapy approach based on proteins, uh,
called neoantigen found specifically in the cancer cell.
Um, we think it's a very, uh, good promise
and also appear very, um, tolerable.
It was not very toxic at all in the earlier, uh, trials done
so far in melanoma.
- Well, it's fascinating to hear
and really encouraging to know
that those early results are coming through.
Um, and, and really something
to be interested and excited about.
Now, I'm wondering, you know,
what are you most excited about in your field?
Obviously, some
of the things you just explained in the phase two trial, um,
really hold a lot of promise,
but what else on the macro level are you
just really looking forward to?
- Thank you for that opportunity.
So in this context, I wanna say that one other, uh,
really exciting finding that's emerging is the value of, uh,
uh, circulating tumor DNA
or CT DNA to select the right patients for,
um, uh, therapy.
So for example, in the adjuvant therapy I just mentioned,
we are actually, um, uh, looking at the CT DNA,
which basically the blood test look to look
for cancer DNA in the blood.
Uh, and so this could really help us, uh,
determine if only patients with the cancer DNA in the blood,
uh, in the postoperative setting have the benefit.
Um, so this is, uh, going to be looked at, um,
once this study is complete.
In this context, I wanna mention
that there is a second adjuvant trial we will
be participating in.
This is called the modern trial.
Uh, the modern trial is a phase three trial,
so it's a much larger trial done
by the US intergroup system.
And basically in this study, patients
who undergone radical cystectomy that removal of the bladder
for high risk muscle invasive bladder cancer, they are, um,
randomized based on whether they have the circulating tumor
DNA or not postoperatively.
So basically, if you have postoperative ctdna, uh,
present in the blood, you randomized to nivolumab,
which is the standard versus, um, uh, nivolumab plus, uh,
a different immunotherapy drug called related map.
This is a lag three inhibiting immunotherapy drug.
So basically we are escalating therapy
to a combination immunotherapy if your CTDNA is positive,
and on the other hand, if your CTDNA is negative, um,
maybe these patients have a much lower risk
of the cancer returning.
So these patients are being randomized
to nivolumab versus surveillance.
And in the surveillance group, when they become CTD NA
or when, or if they become CTDNA positive, then they can,
uh, receive nivo nivolumab.
So really that's, um, a process of deescalating therapy.
So basically CTDNA negative we trying
to watch without giving therapy so
that we avoid unnecessary toxicities in somebody who's not
destining to recur.
So this is another interesting adjuvant trial where the ctd,
NA, um, is being used to select patients
for either escalation by combination therapy
or deescalating, um,
with surveillance if the CTDNA negative,
- That's amazing to hear,
and you know, really exciting, um, to have the, those kinds
of results indefinitely ability to
navigate those clinical trials.
Now, before we wrap up here, I'm wondering
what will the most effective healthcare leaders need in
to be successful in the next two to three years?
Especially looking at your field, um, oncology in research
and innovation, uh,
I can imagine things are changing very quickly.
So what do leaders need to know in order to keep up?
- I think that I will talk in terms of, uh,
the clinical trial landscape, um, uh, in this context.
So basically I think that the clinical trials, um,
have been challenging in the sense
that we have still not maximized, um,
the reach of these trials.
So we know that out in the community there, uh, lots
of patients are not getting access to, uh,
these promising new drugs on clinical trials.
Uh, so the really, the model that needs
to be further developed is to decentralize clinical trials,
make these trials available to anybody in the community.
Uh, that's actually, uh, easier said than done
because in addition to getting these, uh, trials out
to the community, we also need to train our, uh,
clinician medical oncologists out there in the community.
Um, there's a lot of education to be done.
Um, there are a lot of misperceptions out there, uh,
not only among patient, uh, you know, uh,
potential patients, but also among clinicians.
So there's a lot of education to go around, um,
and on on both sides of that.
Uh, in order to improve trial accrual, this is what leads
to further advances with new, uh, new drugs emerging
for patients out there.
So I really hope that this decentralizing model will, uh,
help bring access to the drugs, um,
and will improve all of the,
or reduce all of the disparities we see right now, uh,
with regard to trial access
and access to new promising treatments for advanced, uh,
mostly incurable cancers.
- That's fascinating to hear, you know,
and really great to understand.
Um, when you talk about some of these misconceptions,
is there one that comes up over and over again
or just a, a variety of, um, uh, misconceptions that,
you know, people tend to, um, latch onto?
- Yeah, you know, clinical trials, uh,
are not well understood by, uh, many patients.
And I will also say actually, um, uh,
many clinicians in fact, uh, I think that one of the things
to remember is that clinical trials have the goal of, uh,
evaluating a new, uh, drug.
So there are different phases of, uh, these trials,
phase one, phase two, phase three, and then phase four.
So essentially, uh, one of the misconceptions is that, uh,
the patients worry that they will get, uh, only placebo, uh,
if they get on any trial, uh,
or that they're like a lab rat or something like that.
Now, one of the things I did wanna maybe I could mention
given, since you've given me the opportunity in phase one
trials, um, these are new drugs coming off from the lab.
Everyone gets, uh, the new drug, uh,
and, uh, they're being tested at different doses
to select the right dose for further development.
So there is no placebo involved in a phase one trial.
And, and actually most phase two trials,
which are phase two trials, are when the drug is found,
found to be safe, and we have the right dose from the phase
one trial, they move on to phase two trials to test, uh,
a drug in a specific population of cancer patients, uh,
for example, lung cancer, or you might pick bladder cancer
where there was some activity seen in the,
uh, previous phase one trial.
So in the phase two trial, again,
usually these trials are also, uh, not randomized, uh,
to placebo versus the drug.
Occasionally they might be, um,
however, uh, usually there are, uh, a group of patients
where everyone gets the drug, then we move on
to a phase three trial.
And this is a trial that is, um, designed
to lead towards potential use FDA approval.
So there is a standard treatment versus
experimental treatment.
Now, the standard treatment, um,
sometimes it's placebo when there is no good standard
treatment for these patients, but, uh,
and many of these trials are standard treatment plus
placebo, so they're not just, uh, placebo.
So this is something that the patients need to discuss
with the, uh, investigator to see what the design is.
So, uh, so that's, uh, the difference.
The phase four trials are later stage trials to further,
further assess the efficacy of a, uh,
new drug that's been approved.
And this is, uh, usually also not randomized.
This is a big group of patients who get the drug
to further assess the safety, uh, of the drug in a, uh,
in, out in the community.
So really the, I think that, um, there needs to be a good,
the long discussion between the patient
and the investigator to further clearly, uh,
understand these trials and clear out any misperceptions.
- Amazing. Well, Dr.
Avta, thank you so much for joining us on the podcast today.
This has been, you know, a really fun
and fascinating conversation to hear from you,
and I look forward to connecting with you again soon
and seeing how the results continue to play out.
- Thanks a lot for the opportunity.