Latest / Becker’s Healthcare - Clinical Leadership Podcast / Dr. Guru Sonpavde, Medical Director of Genitourinary Oncology (GU) at AdventHealth Cancer Institute

Transcript

Dr. Guru Sonpavde, Medical Director of Genitourinary Oncology (GU) at AdventHealth Cancer Institute · Becker’s Healthcare - Clinical Leadership Podcast

• 0:00
  - This is Laura Dedo with the Becker's Healthcare Podcast.
• 0:03
  I'm thrilled today to be joined by Dr.
• 0:05
  Guru Sode, who's the medical director of Janitor
• 0:09
  Oncology in the Phase one Cancer Research Unit at Advent
• 0:13
  Health Cancer Institute.
• 0:15
  Dr. Sode, it's a pleasure to have you on the podcast today.
• 0:19
  - Thank you for having me on.
• 0:22
  - Now, I'm looking forward to our discussion.
• 0:24
  I know we're gonna dive deep into some of the
• 0:26
  clinical research that you're doing
• 0:28
  and really exciting work around, uh,
• 0:30
  a new bladder cancer therapy
• 0:32
  and vaccine that is really, you know,
• 0:35
  representing the forefront of, uh, precision oncology.
• 0:39
  But before we dive into that discussion,
• 0:40
  can you tell us a little bit more about, uh,
• 0:43
  yourself and your background?
• 0:46
  - Yeah, thank you for the opportunity.
• 0:48
  So my background is I'm a medical oncologist
• 0:52
  and focused on clinical trials.
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  I have been focused on, um, continuing to urinary cancers,
• 0:59
  which includes, uh, bladder, prostate, and kidney cancer,
• 1:03
  and other, some other urologic system cancers.
• 1:07
  I have primarily been focused on bladder cancer,
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  but at Advent Health,
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  I'm also leading the phase one clinical trial program,
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  which, uh, essentially investigate new drugs coming from
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  the lab into the clinic to, um, look at the safety
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  and the feasibility of, uh, taking the, some
• 1:26
  of these drugs further to treat patients
• 1:28
  with advanced cancers.
• 1:30
  - Well, it's fascinating to hear,
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  and you know, really such a important,
• 1:33
  in rewarding place to be.
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  Now, I know you recently had a trial that you were part
• 1:39
  of get FDA approval.
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  Can you tell us about that trial and treatment?
• 1:43
  - Yes. I was fortunate to be, uh, one of the co-leaders
• 1:47
  of a phase three trial called the Checkmate 9 0 1 trial.
• 1:51
  This is a phase three trial in which had several components.
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  The component that, uh, was, uh, recently in the news
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  and led to the approval of a new drug, um,
• 2:03
  is a component that compared, uh, first line chemotherapy
• 2:07
  with cisplatin and gemcitabine in advanced
• 2:11
  urothelial carcinoma, and that's mostly bladder cancer.
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  Um, although there are patients also
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  with upper urinary tract carcinoma, uh,
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  which had metastasized.
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  So in these patients, um,
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  who are cisplatin eligible fit enough
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  to receive the cisplatin based chemotherapy,
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  the trial compared cisplatin plus gemcitabine, which is the
• 2:32
  standard, which was a standard back then.
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  And this was compared with cisplatin gemcitabine plus
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  nivolumab a PD one inhibitor.
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  So essentially, uh, this combination with nivolumab,
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  the PD one inhibitor, immunotherapy drug,
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  which essentially turns out on the, to fight them
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  and, uh, attack these cancer cells, did lead
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  to an improvement in survival.
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  And this led to us FDA approval for patients, um,
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  who were receiving cisplatin
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  and gemcitabine chemotherapy as first line therapy
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  for advanced urothelial carcinoma.
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  The key highlight of this trial was
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  that there was a 22% complete remission rate, uh,
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  which is the total resolution of all
• 3:16
  of the visible disease on the scans.
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  And the patients who had a complete remission had a very
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  long duration of response within median duration
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  of a little over three years.
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  And so this is, um, um, a promising, uh, finding in, uh,
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  this group of patients.
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  Uh, and this, uh, this data really led
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  to the US FDA approving this combination cisplatin
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  gemcitabine plus nivolumab in patients who were, uh,
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  eligible for cisplatin
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  and had advanced urothelial carcinoma.
• 3:48
  - Well, that's fascinating to hear
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  and really interesting to, um, know that, you know,
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  this type of work is out there and can be so successful.
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  Now, there's also a new phase two trial at Advent Health
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  Cancer Institute located in central Florida
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  that just opened in April for bladder cancer patients.
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  What makes this trial unique
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  and what does this mean for the customized medicine?
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  - Right. We are especially excited about this, uh,
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  new randomized phase two trials that just opened, uh,
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  actually globally and oversight in, uh, Florida.
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  The Advent Health Cancer program is actually the only site,
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  uh, open in Florida and, uh, one
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  of the first sites globally,
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  and the first site in the US to open, actually.
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  So this is the phase two trial,
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  which looks at a different stage of the disease.
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  This is patients who have urothelial carcinoma, um,
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  in the urinary tract that's been removed surgically,
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  but they still have a high risk of recurrence.
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  Uh, so there might be basically microscopic
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  disease somewhere that's not visible yet that might grow
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  with time and, um, then become known as metastatic disease.
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  So in these patients, um, what we know is, um, postoperative
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  or adjuvant nivolumab, uh,
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  PD one inhibitor immunotherapy drug is approved.
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  But what is also known is
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  that very recently the randomized phase three trial called
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  the ambassador trial, uh, showed
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  that there was an improvement also
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  with adjuvant pembrolizumab.
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  Uh, and so pembrolizumab is, um, awaiting us FDA reviews.
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  But what this study is doing here,
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  this is called the inter path 0 0 5 trial.
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  Um, this is a randomized phase two trial, which tries
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  to improve upon the efficacy of pembrolizumab.
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  Uh, so basically patients
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  with high risk urothelial carcinoma who under,
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  who have undergone surgery, are randomized to pembrolizumab,
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  combined with, uh, placebo versus pembrolizumab, combined
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  with the V nine 40, uh, which is the experimental new agent.
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  And I will explain that in a second,
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  but basically what I want to explain is in this trial, uh,
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  nobody is getting only placebo, so all
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  of the patients get pembrolizumab,
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  and one half of the patients, uh,
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  is also receiving the V nine 40,
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  which is given intramuscularly every three
• 6:14
  weeks for nine cycles.
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  So the V nine 40 is an extremely exciting
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  immunotherapy agent.
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  Um, what it is, is it codes for the,
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  um, neoantigens found specifically in the cancer cell.
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  So neoantigen are new proteins
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  found only in the cancer cells
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  because of the mutations found only in the cancer cells.
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  So essentially, when you have, um,
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  a molecule like the V nine 40, which codes
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  for these new proteins
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  or new antigen using the RNA, the corresponding RNA
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  for the these proteins, remember the DNA codes
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  for R-N-A-R-N-A codes for protein.
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  So what, um, um, uh, the sponsoring company has done here,
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  uh, this is Merck in collaboration with Moderna,
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  is made this mRNA immunotherapeutic, which codes for this,
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  uh, up to 34 neoantigens found only in the cancer cell.
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  And this product is, uh,
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  injected into the patient's intramuscularly every three
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  weeks, uh, uh, up to nine times.
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  So this is an extremely specific highly, uh, precise, uh,
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  precision immunotherapy, um, in my judgment, uh,
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  which has been looking very promising
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  so far in a smaller phase two trial, uh,
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  in melanoma a different cancer,
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  there was a significant improvement in the outcomes.
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  And this has led to a phase three trial in melanoma.
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  And really, so this kind of an approach, uh,
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  precision immunotherapy approach based on proteins, uh,
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  called neoantigen found specifically in the cancer cell.
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  Um, we think it's a very, uh, good promise
• 7:56
  and also appear very, um, tolerable.
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  It was not very toxic at all in the earlier, uh, trials done
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  so far in melanoma.
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  - Well, it's fascinating to hear
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  and really encouraging to know
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  that those early results are coming through.
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  Um, and, and really something
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  to be interested and excited about.
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  Now, I'm wondering, you know,
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  what are you most excited about in your field?
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  Obviously, some
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  of the things you just explained in the phase two trial, um,
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  really hold a lot of promise,
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  but what else on the macro level are you
• 8:27
  just really looking forward to?
• 8:30
  - Thank you for that opportunity.
• 8:31
  So in this context, I wanna say that one other, uh,
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  really exciting finding that's emerging is the value of, uh,
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  uh, circulating tumor DNA
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  or CT DNA to select the right patients for,
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  um, uh, therapy.
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  So for example, in the adjuvant therapy I just mentioned,
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  we are actually, um, uh, looking at the CT DNA,
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  which basically the blood test look to look
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  for cancer DNA in the blood.
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  Uh, and so this could really help us, uh,
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  determine if only patients with the cancer DNA in the blood,
• 9:08
  uh, in the postoperative setting have the benefit.
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  Um, so this is, uh, going to be looked at, um,
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  once this study is complete.
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  In this context, I wanna mention
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  that there is a second adjuvant trial we will
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  be participating in.
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  This is called the modern trial.
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  Uh, the modern trial is a phase three trial,
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  so it's a much larger trial done
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  by the US intergroup system.
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  And basically in this study, patients
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  who undergone radical cystectomy that removal of the bladder
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  for high risk muscle invasive bladder cancer, they are, um,
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  randomized based on whether they have the circulating tumor
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  DNA or not postoperatively.
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  So basically, if you have postoperative ctdna, uh,
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  present in the blood, you randomized to nivolumab,
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  which is the standard versus, um, uh, nivolumab plus, uh,
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  a different immunotherapy drug called related map.
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  This is a lag three inhibiting immunotherapy drug.
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  So basically we are escalating therapy
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  to a combination immunotherapy if your CTDNA is positive,
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  and on the other hand, if your CTDNA is negative, um,
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  maybe these patients have a much lower risk
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  of the cancer returning.
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  So these patients are being randomized
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  to nivolumab versus surveillance.
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  And in the surveillance group, when they become CTD NA
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  or when, or if they become CTDNA positive, then they can,
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  uh, receive nivo nivolumab.
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  So really that's, um, a process of deescalating therapy.
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  So basically CTDNA negative we trying
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  to watch without giving therapy so
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  that we avoid unnecessary toxicities in somebody who's not
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  destining to recur.
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  So this is another interesting adjuvant trial where the ctd,
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  NA, um, is being used to select patients
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  for either escalation by combination therapy
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  or deescalating, um,
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  with surveillance if the CTDNA negative,
• 11:03
  - That's amazing to hear,
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  and you know, really exciting, um, to have the, those kinds
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  of results indefinitely ability to
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  navigate those clinical trials.
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  Now, before we wrap up here, I'm wondering
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  what will the most effective healthcare leaders need in
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  to be successful in the next two to three years?
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  Especially looking at your field, um, oncology in research
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  and innovation, uh,
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  I can imagine things are changing very quickly.
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  So what do leaders need to know in order to keep up?
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  - I think that I will talk in terms of, uh,
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  the clinical trial landscape, um, uh, in this context.
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  So basically I think that the clinical trials, um,
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  have been challenging in the sense
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  that we have still not maximized, um,
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  the reach of these trials.
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  So we know that out in the community there, uh, lots
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  of patients are not getting access to, uh,
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  these promising new drugs on clinical trials.
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  Uh, so the really, the model that needs
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  to be further developed is to decentralize clinical trials,
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  make these trials available to anybody in the community.
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  Uh, that's actually, uh, easier said than done
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  because in addition to getting these, uh, trials out
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  to the community, we also need to train our, uh,
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  clinician medical oncologists out there in the community.
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  Um, there's a lot of education to be done.
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  Um, there are a lot of misperceptions out there, uh,
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  not only among patient, uh, you know, uh,
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  potential patients, but also among clinicians.
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  So there's a lot of education to go around, um,
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  and on on both sides of that.
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  Uh, in order to improve trial accrual, this is what leads
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  to further advances with new, uh, new drugs emerging
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  for patients out there.
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  So I really hope that this decentralizing model will, uh,
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  help bring access to the drugs, um,
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  and will improve all of the,
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  or reduce all of the disparities we see right now, uh,
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  with regard to trial access
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  and access to new promising treatments for advanced, uh,
• 13:04
  mostly incurable cancers.
• 13:07
  - That's fascinating to hear, you know,
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  and really great to understand.
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  Um, when you talk about some of these misconceptions,
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  is there one that comes up over and over again
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  or just a, a variety of, um, uh, misconceptions that,
• 13:19
  you know, people tend to, um, latch onto?
• 13:24
  - Yeah, you know, clinical trials, uh,
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  are not well understood by, uh, many patients.
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  And I will also say actually, um, uh,
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  many clinicians in fact, uh, I think that one of the things
• 13:35
  to remember is that clinical trials have the goal of, uh,
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  evaluating a new, uh, drug.
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  So there are different phases of, uh, these trials,
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  phase one, phase two, phase three, and then phase four.
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  So essentially, uh, one of the misconceptions is that, uh,
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  the patients worry that they will get, uh, only placebo, uh,
• 13:55
  if they get on any trial, uh,
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  or that they're like a lab rat or something like that.
• 14:01
  Now, one of the things I did wanna maybe I could mention
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  given, since you've given me the opportunity in phase one
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  trials, um, these are new drugs coming off from the lab.
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  Everyone gets, uh, the new drug, uh,
• 14:13
  and, uh, they're being tested at different doses
• 14:16
  to select the right dose for further development.
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  So there is no placebo involved in a phase one trial.
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  And, and actually most phase two trials,
• 14:23
  which are phase two trials, are when the drug is found,
• 14:26
  found to be safe, and we have the right dose from the phase
• 14:29
  one trial, they move on to phase two trials to test, uh,
• 14:33
  a drug in a specific population of cancer patients, uh,
• 14:36
  for example, lung cancer, or you might pick bladder cancer
• 14:38
  where there was some activity seen in the,
• 14:41
  uh, previous phase one trial.
• 14:43
  So in the phase two trial, again,
• 14:45
  usually these trials are also, uh, not randomized, uh,
• 14:49
  to placebo versus the drug.
• 14:51
  Occasionally they might be, um,
• 14:53
  however, uh, usually there are, uh, a group of patients
• 14:56
  where everyone gets the drug, then we move on
• 14:59
  to a phase three trial.
• 15:00
  And this is a trial that is, um, designed
• 15:02
  to lead towards potential use FDA approval.
• 15:05
  So there is a standard treatment versus
• 15:08
  experimental treatment.
• 15:09
  Now, the standard treatment, um,
• 15:12
  sometimes it's placebo when there is no good standard
• 15:15
  treatment for these patients, but, uh,
• 15:17
  and many of these trials are standard treatment plus
• 15:21
  placebo, so they're not just, uh, placebo.
• 15:24
  So this is something that the patients need to discuss
• 15:26
  with the, uh, investigator to see what the design is.
• 15:29
  So, uh, so that's, uh, the difference.
• 15:33
  The phase four trials are later stage trials to further,
• 15:36
  further assess the efficacy of a, uh,
• 15:39
  new drug that's been approved.
• 15:41
  And this is, uh, usually also not randomized.
• 15:44
  This is a big group of patients who get the drug
• 15:48
  to further assess the safety, uh, of the drug in a, uh,
• 15:53
  in, out in the community.
• 15:55
  So really the, I think that, um, there needs to be a good,
• 15:59
  the long discussion between the patient
• 16:00
  and the investigator to further clearly, uh,
• 16:03
  understand these trials and clear out any misperceptions.
• 16:08
  - Amazing. Well, Dr.
• 16:10
  Avta, thank you so much for joining us on the podcast today.
• 16:12
  This has been, you know, a really fun
• 16:14
  and fascinating conversation to hear from you,
• 16:16
  and I look forward to connecting with you again soon
• 16:18
  and seeing how the results continue to play out.
• 16:21
  - Thanks a lot for the opportunity.