Latest / The Morning Edition / A 'moon landing moment': The new cancer drug therapy that could change medical thinking

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A 'moon landing moment': The new cancer drug therapy that could change medical thinking · The Morning Edition

• 0:04
  S1: It is being hailed as a cancer breakthrough so monumental
• 0:07
  S1: that the lead scientist behind it is describing it as
• 0:10
  S1: a moon landing moment. And not just any scientist, but
• 0:14
  S1: Professor Georgina Long, the Australian oncologist already credited with ushering
• 0:19
  S1: the survival rate of advanced melanoma from 5 to 50%. Now,
• 0:25
  S1: in a world first, a stage three clinical trial led
• 0:28
  S1: by long has shown success in using a personalized therapeutic
• 0:32
  S1: vaccine to dramatically cut the risk of melanoma recurrence and
• 0:37
  S1: death after a tumor is removed. I'm Samantha Selinger Morris,
• 0:41
  S1: and you're listening to Morning Edition from The Age and
• 0:44
  S1: the Sydney Morning Herald. Today, Professor Georgina Long, medical director
• 0:49
  S1: of Melanoma Institute Australia, on when we might have access
• 0:53
  S1: to this treatment and how it might impact the treatment
• 0:56
  S1: of other cancers. Welcome, Georgina to the podcast.
• 1:05
  S2: Thank you Sam, it's a pleasure and an honor to
• 1:07
  S2: be here and talk about something I'm so passionate about.
• 1:10
  S1: Well, we can't wait to get into it with you
• 1:12
  S1: because it is genuinely so exciting. So let's start perhaps
• 1:16
  S1: at the beginning because most Australians would now be aware of,
• 1:19
  S1: you know, the damage that sun can do and its
• 1:21
  S1: links to melanoma. But can you just bring us quickly
• 1:24
  S1: up to speed on how pervasive this disease is here
• 1:28
  S1: and what the survivability rates are?
• 1:31
  S2: Sure. So as many of the listeners would know, Australia's
• 1:35
  S2: cancer is melanoma. We call it Australia's cancer because we
• 1:38
  S2: have one of the highest incidence in the world. We
• 1:41
  S2: have someone die from melanoma every six hours and someone's
• 1:45
  S2: diagnosed with melanoma every 30 minutes. The reason it's common
• 1:49
  S2: is because we have such wonderful UV with sunshine, beautiful sunshine,
• 1:54
  S2: very strong sunshine, high UV and your skin is at
• 1:59
  S2: risk when we expose ourselves to UV. The fairer you are,
• 2:04
  S2: the higher the risk in general. But it doesn't mean
• 2:06
  S2: people with dark skin can't get melanoma. But that's just
• 2:10
  S2: the risk it is. And so with the history of
• 2:13
  S2: Australia and with the migration of a lot of very
• 2:16
  S2: fair people over the last 150 years, when fashion in
• 2:22
  S2: the sort of 1940s, it became very fashionable to start
• 2:27
  S2: wearing bikinis and little trunks and trunks. And so then
• 2:31
  S2: we saw this new, not new disease. It was around
• 2:34
  S2: long before, I think there's a record of melanoma in
• 2:37
  S2: Cleopatra's time, actually, in hieroglyphics. But what happened is we
• 2:42
  S2: saw this uptick in this disease, melanoma in the 50s
• 2:46
  S2: because of people getting their gear off. And then came
• 2:49
  S2: the history of Australians trying to prevent melanoma. But that
• 2:53
  S2: really didn't hit until the 1980s. So that's our history.
• 2:57
  S2: We've still got a problem. We've still got the highest
• 2:59
  S2: incidence in the world.
• 3:00
  S1: And you've led a team that has made what is
• 3:02
  S1: widely reported as a breakthrough in melanoma treatment. So first,
• 3:06
  S1: what does a breakthrough actually mean to you? Because it
• 3:08
  S1: must be something that all scientists strive for in their lives, right?
• 3:13
  S2: My role was the principal investigator for the whole trial
• 3:18
  S2: and also chair of the steering committee for the trial. Yeah. Look,
• 3:22
  S2: breakthrough is a great word, and I think the media
• 3:25
  S2: love a breakthrough. They love a penicillin moment. They love
• 3:30
  S2: a first flight. They love a you know, these these
• 3:33
  S2: cliches to describe something that's very a foundational shift. So
• 3:38
  S2: if I was using a more temperate way to describe it,
• 3:41
  S2: but it is a breakthrough is it's a foundational shift,
• 3:44
  S2: but it doesn't happen overnight. It is founded on lots
• 3:47
  S2: and lots of work. So what is this breakthrough? So
• 3:50
  S2: the first class of drugs over 15 years ago were
• 3:53
  S2: what we call checkpoint inhibitors. Some listeners may know them
• 3:56
  S2: as pembrolizumab. Nivolumab. There's a few others that came after them. Ipilimumab.
• 4:01
  S2: They're the drug names. Those were developed in melanoma. The
• 4:05
  S2: first in humans was in melanoma. Melanoma has led the
• 4:10
  S2: way in how to harness the immune system to kill cancer.
• 4:17
  S2: Very different way of working than chemotherapy, which has been
• 4:22
  S2: around for nearly 100 years, where it kills a wide
• 4:28
  S2: range of cells, including the rapidly dividing cancer cells. But
• 4:32
  S2: immunotherapy is different. The drugs we use do not kill
• 4:37
  S2: the cancer directly. They stimulate the immune system to kill
• 4:42
  S2: the cancer.
• 4:43
  S1: Before we get to the latest breakthrough, which I want
• 4:45
  S1: to get to in just a moment, because you've had
• 4:48
  S1: a previous massive breakthrough before this latest one. So can
• 4:51
  S1: you just briefly tell us about that previous breakthrough? Because
• 4:54
  S1: I believe you are credited with the skyrocketing survival rate
• 4:58
  S1: of advanced melanoma even before this latest breakthrough.
• 5:02
  S2: Yeah, so that's a really good segue, actually, Sam and
• 5:05
  S2: I forgot to say it before when you were asking
• 5:06
  S2: me about melanoma. So we were talking about the highest incidence.
• 5:10
  S2: So why is melanoma so awful? Well, when I started
• 5:13
  S2: in melanoma my waiting rooms often talk about this. If
• 5:17
  S2: you imagine your waiting room full of patients, I would
• 5:20
  S2: see new faces every six months because it was so deadly.
• 5:23
  S2: So melanoma is the deadliest form of skin cancer. Not
• 5:25
  S2: so much anymore, but it was when I started. And
• 5:28
  S2: that's because it likes to spread. By the time a
• 5:31
  S2: patient seen the melanoma, not all the time. If you
• 5:33
  S2: can catch it early enough or it's just a slower
• 5:35
  S2: biological melanoma, it won't spread. But by the time you've
• 5:40
  S2: seen a melanoma, if it wasn't there and then it's
• 5:42
  S2: popped up there over four weeks, that's a very rapidly
• 5:46
  S2: turning over cancer. Often the cancer cells have already escaped
• 5:50
  S2: when cancer cells escape from the primary. So if it's
• 5:53
  S2: on your skin and they land in the lungs or
• 5:56
  S2: the liver or the brain or the bone. It used
• 5:58
  S2: to cause death within 6 to 9 months. So the
• 6:01
  S2: median survival of someone where the melanoma had spread around
• 6:05
  S2: the body. And it did it often, it liked to
• 6:07
  S2: do that by the time it had spread around the body,
• 6:10
  S2: the survival from the time it spread was about 6
• 6:13
  S2: to 9 months. Once we knew it had spread. So
• 6:15
  S2: it was terrible. It was the worst cancer, worse than
• 6:18
  S2: pancreatic cancer. It was the cancer. Did not want to
• 6:22
  S2: get no drugs. Worked until this first breakthrough with what
• 6:27
  S2: we called checkpoint inhibitors, which have gone on to affect lung, kidney,
• 6:31
  S2: bladder cancer, head and neck cancer. Those are the drugs
• 6:34
  S2: I mentioned before. So those drugs cured, we use them
• 6:39
  S2: as single agents, one at a time. Then we put
• 6:41
  S2: them together. This happened over about a decade and we're
• 6:44
  S2: now today where once advanced melanoma 5% would survive five years,
• 6:52
  S2: we're now curing over 50% curing.
• 6:55
  S1: Incredible.
• 6:55
  S2: So in once, yeah, 25% would survive one year. Most
• 7:00
  S2: would die within 6 to 9 months. Now well over 80%
• 7:04
  S2: are going to survive a year and 50% more than 50%
• 7:08
  S2: are cured. Cuit.
• 7:11
  S1: So that's the great foundation from which we can discuss
• 7:14
  S1: the new development, this latest breakthrough by you and your team.
• 7:18
  S1: So tell us about it. You know, what have you achieved?
• 7:21
  S1: Why is the world sitting up and taking notice of
• 7:24
  S1: these particular results?
• 7:26
  S2: So the latest breakthrough was what we call a randomized
• 7:30
  S2: phase three clinical trial. That is where you take a
• 7:34
  S2: patient population in this, it was people who had never
• 7:37
  S2: had treatment for their melanoma before, never. They then had
• 7:41
  S2: their melanoma removed surgically. So they had either what we
• 7:46
  S2: call stage two B to stage four advanced melanoma. There
• 7:50
  S2: weren't many stage four patients. There were mainly two and
• 7:53
  S2: three so early. High risk, high risk. Had it all removed.
• 7:58
  S2: Had a scan, showed that there was no melanoma we
• 8:01
  S2: could see in their body, but we knew they were
• 8:05
  S2: very high risk of it coming back. Like I described before.
• 8:09
  S2: And what we did is we randomized them to a
• 8:12
  S2: standard one year of immunotherapy to mop up any of
• 8:15
  S2: the cells we can't see. That's the pembrolizumab versus pembrolizumab
• 8:22
  S2: plus a personalized therapeutic cancer vaccine. It's another way to
• 8:30
  S2: leverage the immune system against the cancer. So in one
• 8:36
  S2: arm they had the standard one way of of getting
• 8:39
  S2: the immune system to kill the cancer the other. We
• 8:41
  S2: put two drugs together and we saw a reduction in
• 8:45
  S2: the risk of recurring from melanoma or dying from your
• 8:49
  S2: melanoma by 42%. Incredible. Getting the news and hearing that
• 8:57
  S2: hazard ratio, that 42% reduction in the risk. I just
• 9:01
  S2: was blown away because I was not expecting it at
• 9:03
  S2: this first interim analysis.
• 9:05
  S1: Did you cry?
• 9:06
  S2: Yeah, I was I was welled up. Joy. You know
• 9:10
  S2: that joy feeling and your heart starts racing and your
• 9:12
  S2: you get goosebumps and you start jumping around that joy,
• 9:16
  S2: that joy. Because it was proof of principle. The proof
• 9:20
  S2: of concept was just spectacular.
• 9:28
  S1: After the break.
• 9:30
  S2: It's a massive, massive breakthrough. It's setting the bar for
• 9:34
  S2: the rest of the cancers. So there will be studies
• 9:37
  S2: in other cancers using this idea. In technology, it's a
• 9:40
  S2: whole different thinking about cancer.
• 9:53
  S1: So this is pretty incredible. You're talking about a vaccine
• 9:56
  S1: for cancer and it's a personalized vaccine. So tell us
• 9:59
  S1: how this is a personalized vaccine that works, you know,
• 10:03
  S1: on an individualized level for each particular patient?
• 10:07
  S2: Yes. So what we call it, it's a personalized therapeutic vaccine,
• 10:12
  S2: so different to like your measles, mumps, rubella, or any
• 10:16
  S2: of those, even Covid. It's different in that it's not
• 10:20
  S2: preventing the infection. People already have to have the cancer.
• 10:26
  S2: So it's called a therapeutic vaccine. What we do is
• 10:30
  S2: we take the cancer and we take a patient's normal
• 10:34
  S2: cells as well, their blood, and we interrogate and sequence
• 10:38
  S2: the genome, the genetic code of the cancer and the
• 10:42
  S2: normal cells. And we say, what's different? What is in
• 10:45
  S2: this cancer and this cancer alone, that's not an abnormality
• 10:49
  S2: that we can't see in the normal cells. So what
• 10:51
  S2: makes this cancer different from your normal cells then what
• 10:55
  S2: we do, and this is where I want to explain
• 10:57
  S2: the principles of the immune system. So our immune system
• 11:01
  S2: is like the police force of our body. It's there
• 11:06
  S2: to make sure the immune system gets activated against things
• 11:09
  S2: that we need it to get activated against. So your viruses,
• 11:13
  S2: your colds, your covids, your bacteria, if you get any
• 11:17
  S2: sort of infection, you want your immune system to get
• 11:19
  S2: activated to eradicate it. We also want our immune system
• 11:23
  S2: to eradicate cancer because we are producing cancer cells all
• 11:26
  S2: the time, and our immune system is clearing them. So
• 11:30
  S2: our immune system is very complex. It's probably the smartest
• 11:34
  S2: machine in our body. It has got to spend its
• 11:38
  S2: time like the police force working out what is nasty,
• 11:41
  S2: what do I leave alone, what's normal. And so it
• 11:44
  S2: has a lot of pathways that are redundant, lots of
• 11:47
  S2: checks and balances before an immune cell will declare an
• 11:51
  S2: enemy and kill it because you don't want your immune
• 11:55
  S2: system killing all your good stuff. You don't want it
• 11:57
  S2: attacking your eyes. You don't want it attacking your joints,
• 11:59
  S2: your skin. And that's what, for example, psoriasis is. That's
• 12:03
  S2: your immune system attacking your skin. ET cetera. ET cetera.
• 12:06
  S2: But when you have cancer, your immune system has failed
• 12:10
  S2: to see that cancer as a nasty. So what we're
• 12:16
  S2: trying to do with this individualized neoantigen therapy, that's what
• 12:20
  S2: it's called, is discover what's different in the cancer, what's
• 12:24
  S2: different from the normal cells to help that police force.
• 12:28
  S2: And then we choose the top up to 34 neoantigens.
• 12:33
  S2: So these are proteins that are only in the cancer.
• 12:37
  S2: And then we encode them in a little bit of mRNA.
• 12:41
  S2: And we call that the fingerprint of the cancer. Let's
• 12:43
  S2: call that top 34 the fingerprint. We encode the fingerprint
• 12:47
  S2: into a bit of mRNA. We then inject it like
• 12:50
  S2: a vaccine. That little bit of code gets taken up
• 12:54
  S2: by the cells and starts producing the fingerprint. And so
• 12:57
  S2: that allows the police force or the immune cells to go, oh,
• 13:02
  S2: this is abnormal. And it overcomes some of those checks
• 13:05
  S2: and balances. It's like the police force now have the
• 13:08
  S2: fingerprint and a wanted poster and they can say, okay,
• 13:11
  S2: that's a suspect. That is an enemy. So it enhances
• 13:15
  S2: that whole process of the immune system saying enemy, yes,
• 13:20
  S2: you're a friend. No, you're an enemy. I've got to
• 13:22
  S2: get rid of you. And so having this therapeutic cancer
• 13:27
  S2: vaccine of the top specific neoantigens that are only found
• 13:31
  S2: in that individualized cancer, they're not shared by anyone else
• 13:35
  S2: and they're not shared by your normal cells. Enhances that
• 13:38
  S2: immune reaction against the enemy. Plus, we use our standard pembrolizumab,
• 13:44
  S2: which is not personalized. That is a more simple drug
• 13:49
  S2: that just simply interrupts the defense that cancer cells put
• 13:54
  S2: up to prevent the immune system from killing them.
• 13:57
  S1: If this therapeutic vaccine is bespoke for every cancer patient
• 14:02
  S1: because every cancer patient specific cancer is different in terms
• 14:06
  S1: of the abnormal proteins that are on top of that cell,
• 14:09
  S1: does that mean that every vaccine is singular, like the
• 14:13
  S1: tissue gets sent off? And literally that person gets a
• 14:16
  S1: bespoke vaccine. Every single individual person.
• 14:19
  S2: Yes. Yes. It is incredible. And so we've got the
• 14:25
  S2: time down to some patients got their vaccine even at
• 14:29
  S2: three weeks. It's incredible.
• 14:31
  S1: Okay. That's incredible. Can you just tell us a little
• 14:34
  S1: bit about what actually happened to the people who participated
• 14:37
  S1: in this trial for this new development? Because there was
• 14:40
  S1: more than a thousand patients, right, that you trialed with
• 14:43
  S1: this particular treatment.
• 14:44
  S2: So in this trial, it was conducted around the world.
• 14:47
  S2: It was international. There were 157 sites around the world,
• 14:51
  S2: including Melanoma Institute Australia. There were two sites in Sydney, Queensland,
• 14:56
  S2: Western Australia and two in Melbourne, as well as all
• 14:59
  S2: over the world, North America, South America, Europe, etc. so
• 15:06
  S2: over 1700 patients consented and then 1137 were actually randomized.
• 15:15
  S2: And then patients were randomized to the pembro plus a
• 15:18
  S2: placebo vaccine so that they didn't know whether they were
• 15:21
  S2: getting the real vaccine or a placebo, but they were
• 15:24
  S2: definitely getting the standard, the pembrolizumab. And then the other
• 15:27
  S2: group got the vaccine plus pembrolizumab. They were followed. We
• 15:31
  S2: followed these patients. We check for side effects, we do
• 15:35
  S2: scans regularly. And then at a point where we have
• 15:39
  S2: enough data, we then do our first analysis. So this
• 15:43
  S2: is the first analysis. You don't necessarily see a difference
• 15:46
  S2: at the first analysis, but we have 24 months of
• 15:50
  S2: follow up, and we've seen this highly, highly significant reduction
• 15:55
  S2: in the risk of recurrence and death from melanoma in
• 15:58
  S2: the group that got the vaccine plus pembrolizumab. So in
• 16:02
  S2: tisman plus pembrolizumab, 42% reduction in the risk of death
• 16:07
  S2: over pembrolizumab alone. And that's a lot of patients. So
• 16:10
  S2: 757 were randomized to the combo with the actual vaccine,
• 16:15
  S2: 382 the placebo controlled pembrolizumab alone arm. So we randomized
• 16:20
  S2: 2 to 1. We'll be doing more analyses in the
• 16:23
  S2: future because this is just the first analysis. You don't
• 16:26
  S2: necessarily get a positive result at your first analysis. And
• 16:29
  S2: we're going to be watching for overall survival in the
• 16:33
  S2: future as well. So this is the recurrence. We're looking
• 16:36
  S2: for recurrence. And whether people are getting the melanoma spreading.
• 16:40
  S2: And we show that we prevent the melanoma from spreading significantly.
• 16:45
  S1: And you have described this breakthrough as a moon landing moment.
• 16:49
  S1: So is it possible that this vaccine, this treatment could
• 16:52
  S1: be applied to other cancers?
• 16:54
  S2: Yeah, absolutely. That is melanoma's pattern. Anything we've developed in
• 16:58
  S2: melanoma gets rolled out and tested in other cancers. It's
• 17:02
  S2: the way it is because we lead the way in
• 17:04
  S2: these sort of new treatments. So yes, in fact, at
• 17:07
  S2: the conference that I have presented these results, there was
• 17:11
  S2: a presentation on pancreatic cancer there moving through behind us.
• 17:15
  S2: In fact, the reason this trial was so significant, it's
• 17:19
  S2: the cherry on the top. It is a phase three
• 17:21
  S2: randomized controlled trial. It is the final plank in evidence
• 17:25
  S2: to show something works before you then have health authorities
• 17:30
  S2: consider drugs for their population. You need a randomized phase
• 17:34
  S2: three trial. The other beauty of this trial. Why is
• 17:36
  S2: it a moon landing? Why does first flight it really
• 17:40
  S2: it's like what email did to communication. It's that a
• 17:43
  S2: bigger leap? It is the first trial to show that
• 17:49
  S2: an mRNA technology. This is the first one using mRNA
• 17:53
  S2: in cancer works. It is the first trial to show
• 17:59
  S2: that the personalized vaccine approach. Because the mRNA platform you
• 18:03
  S2: can use for all sorts of drugs. But so the
• 18:05
  S2: platform worked in cancer and also that personalized fingerprint exposing
• 18:12
  S2: your immune system to that neoantigen fingerprint works. So first
• 18:16
  S2: personalized vaccine. That's the second thing. And also it is
• 18:21
  S2: the first trial in the adjuvant setting. So when you've
• 18:25
  S2: already removed all the cancer to add something to pembro
• 18:30
  S2: and make a difference, because we've done three failed phase
• 18:34
  S2: three trials in this same population using either pembro or nivolumab,
• 18:40
  S2: adding a second immune treatment to it. And they all failed.
• 18:44
  S2: So these are three big firsts. First, personalized vaccine using
• 18:49
  S2: Neoantigen fingerprint. First mRNA cancer trial to show the platform
• 18:55
  S2: works beautifully. First trial in melanoma in the mop up
• 19:00
  S2: adjuvant setting. To build upon pembrolizumab or that anti-pd1 checkpoints
• 19:06
  S2: that are used in all the other cancers now after melanoma.
• 19:09
  S2: So it's a massive, massive breakthrough. It's setting the bar
• 19:13
  S2: for the rest of the cancers. So there will be
• 19:16
  S2: studies in other cancers using this idea and technology. It's
• 19:20
  S2: a whole different thinking about cancer. It's enhancing that whole
• 19:25
  S2: pathway and journey we've been on for the last many decades,
• 19:30
  S2: but particularly the last 15 years of, of, of getting
• 19:34
  S2: the immune system to kill the cancer, not the drug.
• 19:37
  S1: But just to wrap up on this current breakthrough, this
• 19:40
  S1: incredible personalized therapeutic Vaccine. You have just done the stage
• 19:45
  S1: three clinical trial. What happens from here, you know. Is
• 19:48
  S1: it possible this will become available to Australians soon? Or
• 19:53
  S1: how long will it take before it's available to patients here?
• 19:56
  S2: Yeah. So that's a good future question. So number one,
• 20:00
  S2: all the health authorities around the world will scrutinise the
• 20:02
  S2: data that gets presented to the TGA in Australia, the
• 20:05
  S2: Therapeutic Goods Administration, then to the Pbac, the Pharmaceutical Benefits
• 20:10
  S2: Committee that then look at the data, and then they
• 20:13
  S2: decide whether it goes on the PBS for all Australians
• 20:16
  S2: that fit the criteria, though, this trial was conducted in
• 20:20
  S2: stage two and three patients, so it's not for everyone.
• 20:24
  S2: That process takes anywhere from 12 months to three years
• 20:29
  S2: to look at the data and look at the cost
• 20:32
  S2: benefit analysis and all of those things to decide whether
• 20:37
  S2: this is worthy of us Australians paying for. Because it's not.
• 20:41
  S2: When we say the government pay for it's us, it's us.
• 20:44
  S2: It's our money, it's our tax. So that process will
• 20:47
  S2: be in train around the world. The other part of
• 20:50
  S2: the future is we have an ongoing trial in advanced melanoma.
• 20:53
  S2: So back to the stage four group where they have
• 20:56
  S2: active melanoma. That's called the Interpath. Those results aren't ready
• 21:00
  S2: yet but they will come out in the future. My
• 21:03
  S2: passion that third space in cancer. And that's the group
• 21:06
  S2: of patients who are still dying of melanoma. Because what
• 21:09
  S2: we learn there impacts lots of other cancers. And so
• 21:12
  S2: that's what Melanoma Institute Australia, we're very focused on trying
• 21:16
  S2: to cure all people with melanoma. Zero deaths. And we
• 21:21
  S2: call the group that none of these drugs are working
• 21:23
  S2: on the third space. And we're working on getting those
• 21:26
  S2: people onto clinical trials earlier and earlier in their journey.
• 21:38
  S1: Wow, what an exciting breakthrough. I'll definitely be watching it
• 21:42
  S1: closely as it moves through the relative agencies that now
• 21:45
  S1: sort of take it hopefully to the next stage. So
• 21:48
  S1: thank you so much, Georgina, for your time.
• 21:51
  S2: Thank you Sam, it's been a pleasure and thank you
• 21:53
  S2: for asking some fabulous questions about this incredible transformational shift
• 21:59
  S2: in cancer. Thank you. Thanks for having me.
• 22:20
  S1: Today's episode was produced by Josh towers. Our executive producer
• 22:24
  S1: is Tammy Mills, and our podcasts are overseen by Lisa
• 22:28
  S1: Muxworthy and Tom McKendrick. If you like our show, follow
• 22:32
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• 22:34
  S1: Apple or Spotify. Thanks for listening.