Advancing oncology trials in Asia-Pacific

Although Novotech doesn’t specialise in any specific therapeutic indication, oncology makes up approximately 40% of our trial workload.  We’ve conducted close to 300 oncology studies and our oncology experience ranges across all phases of clinical trials and all types of therapies.  Being a biotech specialist CRO, the majority of studies are in the early phase, ranging from First-in-Human to phase II.  Novotech has also been proud to have supported a number of successful registration studies across the region.  Over recent years, it’s been very exciting to see our biotech sponsors progress through the early phase of development of their studies to the phase III setting.  Our experience very much reflects the biotech landscape.  Our early trials included chemotherapy as investigational agents, which then moved into targeted therapies and more recently, immunotherapies including cell therapeutics and gene therapy.

According to GlobalData, close to 50% of all oncology trials do have an APAC component.  There’s been a strong and continual growth in the number of industry sponsored trials being initiated in Asia-Pacific over recent years.  We’ve definitely seen that trend grow at Novotech.  And personally, I found that some of our sponsors initially may have been apprehensive to considering APAC due to the fact that it is an unknown or unfamiliar territory.  But once they have developed their confidence in the region and experience success with their study, the decision to continue their clinical development in APAC is a much easier one.

We did receive many questions from today’s webinar’s attendees regarding the impact of COVID with our ongoing studies in Asia-Pacific, so we felt that we needed to specifically address this.  And we were really interested to see that a survey that was conducted by the Cancer Research Institute was an independent survey and it identified that our Asian centres had significantly less disruption to their ongoing oncology clinical studies as compared to the US.  Only 40% of our Asian centres indicated disruption to their studies as compared to up to 80% of US sites.  And we really have seen that our Asia-Pacific centres have been able to progress through that initial pandemic stage, our centres across the region, and particular in locations such as Korea, Taiwan, we’ve seen centres very much get back to original activities.  Our centres in Australia again, are opening up and progressing through to normal trial activity.  During those initial phases where there was concern with COVID, a majority of our centres were able to support virtual monitoring and electronic monitoring of the data, so we felt that we were able to continue with our ongoing trial activities with minimal disruption. 

At this point, I’d now like to ask Helen Collins from Five Prime to share with us her company’s experience in the APAC region.  Thanks, Helen.

Dr Helen Collins: Thank you very much.  And thank you so much for asking me to speak today because we’ve really had, our company, an excellent experience in, both with you and also just in other trials that we’ve enrolled in the Asia-Pacific region.  I’m the Chief Medical Officer at Five Prime, so we are a small biotech based in South San Francisco.  And as you can see on the slide, I’ve been around for some number of years.  The goal of our company is to develop novel immuno-oncology drugs.  And we had previously done a – before we were in contact with Novotech, had previously done a Phase I in gastric cancer, so that had included, by virtue of the type of disease it was, some sites that were in South Korean in particular.  And so we’d had experience with excellent care that the patients received there and excellent engagement with the investigators, so we were somewhat in favour of considering this when we were – how we came in contact with Novotech.  

But the particular trial that we’re doing with Novotech is interesting in that it’s a novel IO drug with a mechanism of action that can tell you, made the FDA and other regulatory agencies somewhat anxious.  You can see here that the trial opened in October of 2018 and has been going on for some time, but that’s because we had to start at such an exquisitely low dose that so far, this trial has had 11 cohorts.  And so I think what this slide doesn’t speak to, is how quickly and how well run this trial has been.  

To be clear, the things that we are looking for as a small biotech company are – the most important thing is engaged investigators, investigators that are really interested in how the drug might work, the mechanism of action, making sure that the right patients get put on because, as we all know nowadays, even though phase I trial is for safety, people are expecting to see efficacy during that phase I as well.  And then the other thing is, again the engagement with the sites, because these are novel drugs and we need that feedback, to say what do they think is working, what do they think is not working, what kind of amendments might we need to do, what changes to the trial.  The third thing is that we need to work with our CRO on our sites to make sure that we stay on schedule, and that’s absolutely been our experience throughout these 18 months.  And then the final part is the science part, so there’s a component of these phase I trials, as you may all know, in terms of biomarkers and really making sure that the sites are following these sometimes very complicated protocols to the T, and I think on all four of those, we’ve just been beyond thrilled, aside from the whole COVID, that we’ve been able to stay on schedule.  

I’m trying to think if there’s anything – I think that kind of hits our experience.  Again, I think the biggest difference between the APAC and, say US sites, again is really that strong engagement by the investigators and the sites in terms of enrolling the right patients for your drug based on the proposed mechanism of action.

Julie Gargano: Thanks, Helen.  Moving now to our investigators.  I would like to ask Professor Lee from Samsung Medical Centre to share with us her experience and her team’s experience with oncology studies in South Korea.  Thank you, Professor Lee.

Prof. Lee Jee Yun: Thank you inviting me to this webinar.  I’m a Medical Oncologist working at Samsung Medical Centre, and our centre has been one of the active sites to work with Novotech as well as biotech companies in the past few years.  Samsung Medical Centre is one of the top three big centres in Korea with 10,000 daily outpatients, of which 800 patients are oncology outpatients.  We have 2,000 beds, 1,500 clinical trials, and 800 clinical trials are oncology trials.  And we have over 300 nurses and physicians dedicated to oncology practise.  We have been involved in over 100 phase I oncology trials, mostly sponsored by global pharma, such as AstraZeneca, Merck (MSD) Lilly or Roche, to name a few.  And we are active recruiting sites for US biotech companies such as ALX Oncology, Five Prime, Incyte, Halozyme, to name a few.  

The strength of our centre is that we have an NGS platform implemented in oncology practise.  In Korea, NGS is reimbursed by the National Insurance system nationwide in metastatic disease.  We have the largest hospital based clinical sequencing facility in Korea that is implemented in the hospital, which is very important, and so this is now research based.  We have 11 NGS facilities, such as Novaseq, HiSEQ, NEXTSEQ, MiSEQ and over 10 Bioinformaticians, so in light of this, not only we are actively involved in clinical trials with US biotechs, but we are also actively involved with biotech companies around the world for NGS based biomarker exploratory studies, either in real world or a clinical setting in the past few years.  It has been really a great experience with Novotech as well as US biotech companies.  And I think one of the great experiences, and thrilling experience that I had was the close communication when compared to global pharma’s large trials.  We worked closely with CROs and also sponsors, so that we maintained close communications while we enrol patients, especially in early phase I trials.  

Julie Gargano: Thank you, Professor Lee.  We really have seen so much engagement from our South Korean investigators and centres, and particularly in these early phase trials.  From my perspective, being involved and supporting feasibility for our study sponsors, when we’ve reached out to many of our South Korean centres to be able to receive such high-quality feasibility data quickly as a result of having very detailed databases available of your study patients, has been extremely helpful.  I remember some of our early studies, we were looking at feasibility of a hepatocellular carcinoma study and one of our centres in Korea indicated that they saw 500-plus HCC patients per year.  And I actually went back to that investigator to confirm, was it a typo, to see so many patients.  And in fact, that was correct, so we’re really lucky to have such excellent centres and the ability to access large numbers of patients, in particular, in some of those specific oncology indications that are more prevalent across the Asia region.  So thank you very much, Professor Lee.  

I’d like to ask Ben Tran, Dr Ben Tran from the Peter MacCallum Cancer Centre, closer to home, based in Melbourne, Australia.  Ben, thank you.

Dr Ben Tran: Thanks for the invitation, Julie, to speak today.  It’s a real pleasure to be able to promote the Asia-Pacific region.  As many of you may know, Peter MacCallum Cancer Centre is Australia’s largest and, what we would consider, the premier cancer centre within our country.  We are world class investigators across all tumour streams and have had the pleasure of being able to take new drugs from phase I all the way to Phase III and registration.  Within our cancer centre also sits what we believe is a world class research facility.  And we’re also able to take drugs that are discovered and worked up in the laboratory and take them into the clinic.  

Peter MacCallum is also lucky enough to be part of big pharma alliances.  We’ve been invited to be participants within some of the alliances of our big pharma partners and we’ve been active members in trying to advance the field of oncology with them.  Peter MacCallum Cancer Centre moved to the current Parkville precinct, which sits just above the central business district in Melbourne, Australia about four years ago.  And we see this precinct as almost like moulded upon the Longwood district in Boston, so we have the cancer centre, we have the Royal Melbourne Hospital, the University of Melbourne, along with the Doherty Institute, which has been really critical in a lot of the research around COVID-19.  And just up the road is the Royal Children’s Hospital.  

As Peter MacCallum came to this precinct, we created the Parkville Cancer Clinical Trials Unit, which is Australia’s largest cancer trials unit.  It incorporates the Peter MacCallum Cancer Trials, the Royal Melbourne Cancer Trials and that of the Royal Women’s as well.  It’s a very large unit, as I said; 85 EFT research staff, we utilise two HREC Committees, which are very experienced in early phase studies.  And we have a median time of submission to governance approval of around 89 days, but are able to turn that around quickly where necessary with a minimum of 65 days.  You can see there, that although we have ongoing completed studies of around 450, we do have around 220 ongoing studies right now.  We actively recruit over 500 patients each year.  And we’re a team-based model with 10 teams, which include 12 tumour streams and an Early Drug Development Unit, which kind of oversees or sits overlapping with many of the tumour streams.  

We work very heavily within Cancer Trials Australia.  Cancer Trials Australia is able to engage sponsors to access coordinated clinical network and advice on clinical trial design and incorporates 30 members across the country.  One of the benefits of Cancer Trials Australia is the set up to conduct First-Time-In-Human studies without an IND, so we’re able to submit to ethics and at the same time, go through a scientific review to ensure the drugs are safe to proceed.  

Our phase I program or phase I network within Cancer Trials Australia is very experienced.  We’re able to provide input, […] design and this happens on a regular basis as biotech approaches us.  Although we work a lot with big pharma, we find working with biotech very interesting.  We find that we’re able to contribute quite significantly to the development of the drug and hopefully towards its success.  Big thanks for having me, Julie.

Julie Gargano: Thank you, Ben.  And I must say, I have been very proud to show and introduce many of our biotech sponsors to the Peter MacCallum Cancer Institute and they have been so impressed with the facilities.  Many people have assimilated the building to look like the Guggenheim Museum in New York, very impressive.  But in particular, just the resources that you have on site, we know the Peter MacCallum also houses cell therapies, which is Australia’s largest and commercially producing cell therapies products now.  Also, Peter Mac has been leading the way with our cell therapy trials across Australia.  You also house Nexomics, which is a fantastic laboratory that we have used for many central assessments and assays that are very specific to oncology.  And obviously the team at Peter Mac are just so approachable.  It’s sometimes quite daunting speaking to such high calibre experts, but very much down to earth and so happy to support and assist us with our trials.  So thank you, Ben.

I’d now like to ask Dr Amy Prawira from St Vincent’s Hospital, part of the Kinghorn Cancer Centre in Sydney, to provide us with an overview of her centre.  Thank you.

Dr Amy Prawira: Thanks, Julie, for the introduction and thanks to Novotech and Endpoints News for organising this webinar.  I am a staff Medical Oncologist at St Vincent’s Hospital, Sydney, the Kinghorn Cancer Centre.  The phase I clinical trials unit in our centre, we have over 150 ongoing oncology clinical trials and we are the largest early phase clinical trials unit in New South Wales.  Out of the 150, about 40 are early phase clinical trials in solid tumours.  We are proud to have been successful in enrolling […] first visit for a number of our global pharma studies and certainly, personally having worked in early phase clinical trials in North America, it’s been great to be able to return home to Australia and to continue to work in early phase clinical trials. There is great collaborations with the Australian counterparts of global CRO, such as Novotech, and also, with the Australian counterparts of global pharma companies. It has been very rewarding, as Ben said, to have been involved in developing novel molecules where we help refine the study design, sometimes taking them through […] applications, develop the protocol and certainly to be involved in the conduct of the clinical trials itself.  

We are a founding member also of the NECTA alliance, which is the New South Wales Early Phase Clinical Trials Alliance.  It was founded about five years ago.  It is a consortium of six sites across New South Wales, soon to be seven, and it’s a centralised hub which shares expertise and also cross-refer patients.  Across the six sites, we currently have over 115 ongoing early phase clinical trials.  And certainly, one of the issues that is very important to me is being able to match patients to the right trials, and I find the NECTA alliance is very helpful in that case because we have a database of ongoing clinical trials.  We also have a centralised email address, which is clinicaltrials@necta.org.au, where once you send an email there, there’s a block email to representatives from all of the sites, so with one email, we’d be able to know which slots are available to try to match patients to the best or the most – the best match scientifically at least, if not better clinical trials that’s available at that time.  Back to you, Julie. 

Julie Gargano: Thank you, Amy.  And I must say, having worked on many studies with the NECTA group and seeing that close collaboration between all investigators from NECTA and the centres has been a key to the successful recruitment and also supporting us in making sure that we’re able to identify the best sites from within the NECTA to not only recruit well but also give us those streamlined start-up timelines that we often need.  The government incentive that has now been introduced to allow those phase I First-In-Human Studies to be submitted to a private ethics committee called Bellberry has very much supported that rapid start-up of First-In-Human studies in New South Wales public centres.  And something across the board that we really do see within Australia is that very close collaboration of investigators and centres, so although a patient may not have access to a trial that their oncologist is running, we have many clinical trial referral apps that both patients and oncologists have access to, to support that cross-referral and inter-patient referral for the clinical studies.  Thank you very much, Amy.  

And I believe we will now move into our question and answer portion of the webinar.  We’ve had some fantastic discussion and I now wanted to move into the Q&A session.  We really have received a large number of questions from our registrants and we will aim to answer as many of those questions as we can during our webinar today.  If we are unable to answer all questions, we will be very happy to follow up with these questions after the webinar.

I really would like to make this Q&A session as interactive as possible and encourage active discussion amongst all our panellists.  I might start by asking Helen, as a sponsor representative, this first question.  

Question: And it’s a question that has come from a number of registrants, and it’s in reference to the process of running studies in Asia-Pacific and, in particular, how this process differs from North America.  Helen, I’d really like to ask for your perspective on how the process of involving science in APAC does differ from North America and what the challenges faced by sponsors in the region.  Thank you.

Dr Helen Collins: I think when we started to, or made this proposal that we would be doing in particular this very important phase I for our company in the APAC region and with Novotech, there was a fair amount of anxiety, I can say not just in my clinical development team here in South San Francisco, but even from our management team in our company and even some board members, because we try and stay on a budget and it’s far away and somehow, if you want to say, it must be different there.  And I can say that I think I speak for everybody on our team and our company, that that was not the experience.  The setting up phone calls, certainly they’re done in the afternoon, in the evening, because it’s the far east’s morning.  In some ways, that’s actually easier because again, in pharma, people like to work in their 8-5, 8-6 time range.  And then, as you know, the physicians on the phone here, you have patients during that time.  And so, having a morning call can be easier, or an evening call.  So if anything, we actually found, for example, getting investigators on the phone has been simpler because of the time change.  

And I think we keep hitting it as the common theme, but it really is, as I said, the interactions with the investigators that just makes the difference for a phase I trial.  I mean we all want these drugs to succeed, but we also, if they aren’t going to succeed, we want them to fail quickly.  And the only way you know which path you’re on is if those investigators are knowledgeable investigators doing lots of phase I trials and they’re constantly telling you, here’s what we see, here’s what we think, here’s how we think you should change your trial, here’s how standard of care is changing and so you’re going after the wrong patient population.  And we sit in our bubble, we ask people what they think, but you really rely on those investigators.  And that’s just been the best experience.  You don’t have – and I don’t want to disparage some of the wonderful US phase I sites we’ve worked at, but there is a slight qualitative difference in some of those US sites of we just move the patients through, we move the patients through and check off the numbers.  And that’s not what you get with the APAC sites.  You really do get a sense that people really want to put the right patient on for the patient’s sake, which again is going to be best for your drug.

Julie Gargano: Thank you, Helen.  That’s very pleasing to know and obviously having been working in the area of oncology, I think that’s one of my greatest areas where I highly endorse our APAC investigators, that collaboration and making sure that the patient is referred to the best trial for their situation and disease is so highly regarded.  Thank you.  

Question: Just progressing a little bit more from that, another question that we often hear, and we did receive through this webinar is the acceptability of data from the Asia-Pacific region.  We totally understand that in many of our biotech companies, their priority is to ensure that their data can be submitted and accepted by health authorities, whether that be North American, European, and I suppose also acceptance by potential investors, etcetera.  Could you tell us a little bit about your thoughts on that and whether there’s any challenges or pushbacks?

Dr Helen Collins: Yeah, so I think the regulatory one, again, I hinted at that when I spoke on our Five Prime slide, that we as a company had had an experience of doing a phase I study that was primarily enrolled actually in South Korea and then used that data to globally approach regulatory agencies in almost 20 different countries, of course US, Europe, Mainland China, and use that data to support starting a phase III trial and had absolutely no questions about the quality of the data.  And even when we put it as specific questions; Are you concerned that there’s – and universally not, I think our experience was that the data is thought to be as high quality as anywhere.  

In terms of the investors and analysts; I feel like there’s two parts to it.  One is that, no, we don’t get questions – I spend a lot of my time, probably every week a couple of analysts or investors that I’m speaking to along with our CEO, there’s no concern or question about where, and in particular our phase I trial being run in the APAC region.  We do internally want to be sure; we do think that should our drug be successful, that there is some merit in having US opinion leaders aware of the drugs and at some point, some experience.  So we certainly have set up our trials, that once we get through the dose escalation, if we’re going to start expanding, we will have some US sites on board.  But again, that is more our internal anxiety.  I cannot point to any data to say that.  We use US investigators or opinion leaders, if you will, as consultants, so that obviously under CDA we talk to them about our data and, not surprisingly, they don’t tell us anything differently than what we’re told by our investigators themselves in Australia and South Korea.  But again, as a way to make sure that they’re engaged and aware of the drug that we’re developing.  The short answer is no, but I would be lying if I didn’t say that there’s a little bit of internal anxiety.  We’re often asking about it and we’re making sure that we cover that by keeping some people in the loop that are in the US.

Julie Gargano: Sure.  Thank you, Helen.  That was really helpful.  I’d like to move to some investigator directed questions now.  And perhaps if I start with Professor Lee. 

Question: Professor Lee, what’s Samsung’s experience in conducting oncology trials with biotech sponsors?  And where do the bulk of these sponsors come from?

Prof. Lee Jee Yun: We have a great experience with US biotech sponsors.  We either get contacted directly or through CROs, like yourselves.  I think Novotech is one of the active site’s CROs to introduce biotech companies to Samsung Medical Centre.  I think one of the reasons – there has to be a reason why they want to do clinical trials overseas, and I think one of the reasons they contacted us was the incidents-wise.  We have different incidents of cancer types, like cancer types like gastric hematoma, biliary rare cancers.  Specific types of melanoma that we see here is different in US melanoma patients.  I think there has to be a strong reason why they would come to us and open a trial here.  And I think the top reason was the type of disease that we see here and also, if you’re going after a rare genomic aberration, that’s where we can do well in because it is merged with the high patient volume that we see at our centre.  If it is like FGFR2 amplification in gastric, the incidence is really low, like 2%.  But if you’re seeing 500 patients per year, then you’ll have a good number to enrol.  

And while you’re doing that, no one really knows – not no one, but there is a grey zone of how to define that genomic aberration, whether it’s going to work or not, how high the copy number should be if you’re considering that patient as a right patient.  And that’s when the close communication with biotechs and investigators are important.  And that’s how we handled our oncology trials, especially with biotechs.  Not always, but sometimes, usually if it is global big pharmas, hard to communicate, even though you have the answer maybe.  I’m a strong believer that answers do come from clinicians and the clinic and patients.  I think that’s the attractive point for investigators.  Everyone’s busy.  Investigators are busy, and companies are busy as well, but that’s when the attractive sparkling point happens.  It’s been a great experience.

Julie Gargano: Very pleased to hear the successful experience you’ve had, and I’ve also seen the success of including South Korea and even some of our other APAC countries when we look at, in particular, some of the newer therapies, where we often find that North America, for example, has access to the newer therapies.  And when we are looking at these early phase studies, having access to patients that are either naïve to these therapies or don’t have access to these therapies, such as IO therapies, has been a huge drawcard and a real driver of recruitment across the region.  We work very closely with our sponsors and our investigators to help devise the best strategy of where these patients can be identified to support a study.  Thank you, Professor Lee.  

I wanted to move a bit closer to home to Australia.  And Ben, I might start with you.  

Question: Peter MacCallum, a very highly regarded and sought-after centre when it comes to ecology studies here in Australia.  I’d be really interested to understand what the process for selecting which studies are taken on by the Peter Mac team and how do you handle the competition between these studies.

Dr Ben Tran: Thanks, Julie.  I might start by speaking about phase III studies and the later phase studies briefly and then I’m going to move quickly into the early phase studies.  When it comes to selecting phase III studies, it’s really academic interest.  Do we have the leadership roles in these large studies, and do we have the patient population that we can recruit to?  Is there resource?  Are there competing studies?  When there’s a very large population, for instance in castrate-resistant prostate cancer, I lead the GU group here at Peter Mac.  We can conduct competing studies because we can recruit very well to both studies with such a large population.  When it’s a more niche population, for instance in testicular cancer, it may be that we only open one study in that space.  When it comes to early drug development, we always prefer to be approached earlier by biotech or pharma.  We feel we have an expertise and a knowledge that we can add significant value to helping workup drugs, in developing protocols in selecting the right patient population, in even guiding the translational studies that may be built around those protocols.  

As you can imagine, we’re approached by many biotech and large pharma about new drugs that they want to take to us, that they want to consider us as a site.  And we now have a process that we’re able to review our interest in that very rapidly.  We have a small team that’s able to review the IB, review the protocol, see where it sits within our portfolio, see where it sits now and moving into the future, and select based upon that.  And if we’re not able to participate or not able to provide any feedback or participate in the study longer-term, we kind of feed that back directly and very quickly.  We always prefer to be involved in the dose escalation of early phase studies.  We don’t like to join in dose expansion unless it’s something that we’re very passionate about.  And as I said, by being approached early, we feel as though we’re part of that drug’s development.  And in doing so, that kind of builds our ability to guide and shape the development of each individual drug.

Julie Gargano: Thank you, Ben.  And I, again, have seen that, I know the team at Peter Mac very much want to collaborate with our study sponsors, not just a study site referring patients, but very much a team effort.  And obviously having so much expertise is a huge bonus to our sponsors.  Thank you very much.

Question: Moving across to another question, along the lines of recruitment again.  And this question has come from a number of our participants.  Many of our sponsors ask about recruitment potential and recruitment rates in Australia given our small population.  I might start by asking Amy, and then Ben, please feel free to provide any additional input as to what are the major challenges in the recruitment of patients to oncology trials, and how do each of your centres manage these challenges to facilitate recruitment?  Thank you.

Dr Amy Prawira: I guess overall, I find that Australian patients and Australian Medical Oncologists are really well informed.  And clinical trials is pretty much accepted as another potential treatment option in the spectrum of potential treatment options that cancer patients have.  In fact, in our centre, recruitment, we haven’t found it to be a particular challenge.  But I guess one thing that people might find is a bit unique to Australia is that specialised care tends to be centralised in the metropolitan area, so that a number of our patients do come from rural and regional centres, so when it comes to early phase clinical trials, then the question becomes; what do you do when they become unwell?  One of the ways that our centre manages this is by providing patients with a 24/7 number to call, so that during hours they’ll be contacting our nurses, but after hours, weekends and public holidays, they have access to the personal mobile numbers of at least two staff Medical Oncologists, including myself, so that we can help direct the local team, tell them what these numbers and letters are, what these drugs are, what the potential side effects are and potentially organise early transfer to our centre if need be.  But in fact, I find that with the whole COVID situation, our waiting list of patients has grown quite significantly because a number of clinical trials have gone on global hold in terms of slots.  We have more patients than we have slots for.

Julie Gargano: Thanks, Amy.  And again, feedback that we often hear is that patients want to support clinical trials, they’re made to feel even more special, that close monitoring and follow up and support that the study team, the research nurses provide is very helpful to patients.  That’s great to see.  And, Ben, did you having any further comments to add?

Dr Ben Tran: Yeah, I guess it’s important to note that most of Australia’s population lives in big cities, so unlike the United States, where there are smaller cities, smaller towns, any cancer centre like Amy’s or ours that sit in large cities have quite a significant recruitment and catchment area and captures quite a large number of patients.  We also have very strong networks within the private sector, so that patients coming through the private sector are also considered for our trials as well.

Julie Gargano: Thanks, Ben.  I’m going to move back and ask Professor Lee and Helen if they can comment.  

Question: Perhaps the most common questions that we received from registrants for our webinar was in relation to the COVID pandemic and the clinical trial situation across Asia-Pacific and potential disruption to clinical trials.  Professor Lee, I wanted to ask how the COVID situation has affected your site and activity and career, and then move on and ask Helen if she could provide some feedback from sponsors’ perspective, how her studies in Asia-Pacific have been managed through the pandemic and then, has there been any differences between the US and APAC in this regard.  So, Professor Lee, if I could ask you to start?  Professor Lee, I think you’re on mute.

Prof. Lee Jee Yun: COVID-19, I think every oncologist around the world is extremely nervous about it.  When the pandemic began, we were on the conservative side to enrol oncology patients, especially high-risk clinical trials.  COVID-19 is not a separate thing that is controlled by the hospital.  It’s a governmental nationwide type of effort to control COVID-19.  So far, we are minimally affected by COVID-19 for oncology trials because nationwide incidents, is not very high right now.  We are continuing to see about 40-50 patients per day, new cases, but we do over 20,000 tests per day as well, so the present positivity is less than 0.5%.  With that number, I think we start to pick up on enrolling patients and, as you see, it’s a community-based disease, so oncology patients are extremely cautious.  They don’t go outside and they pretty much lock themselves out, so they don’t get interrupted chemotherapy or lose the chance of clinical trials.  I think at this point, I’m pretty confident to say that we are less concerned about COVID-19 when we are enrolling patients for oncology trials.

Julie Gargano: Thank you, Professor Lee.  And again, I agree that, I think it was South Korea that was one of our first countries that actually went back to almost business as usual practice during the pandemic.  Helen, could I ask you to share your experiences, or Five Prime’s experiences with the ongoing-----?

Dr Helen Collins: Yeah, so I think where Dr Lee is at, is that there has not been a change in terms of our trial that’s been run in APAC through Novotech, it is as if COVID doesn’t exist from our perspective in terms of enrolment and every step along the way.  That is not true of trials that we have running elsewhere.  Again, I think it is, as Dr Lee said, sort of – you’ve heard around the commitment to quality and how well organised the sites are as well.

Julie Gargano: Great to hear, thank you.  Just changing gear a little bit, and again, moving to our three investigators.  

Question: I wanted to ask each of you if you could provide us with your thoughts on some of the newer and innovative trials and therapies that your centres are either participating in or planning to participate in and the future direction of the therapies.  Perhaps I might start with Ben, if you could share some of your experience.

Dr Ben Tran: Thanks, Julie.  It’s been great to work in oncology and see the field move so rapidly over the years.  When I first started out, it was the targeted therapies era, and that moved quickly into a precision oncology era.  We’ve built up a significant capacity to profile patients regularly and identify actionable aberrations that we can target.  And then now, we’ve moved into the IO era and we’ve gone through basic checkpoint inhibitors all the way through to more novel bispecific approaches, which we’re very excited about.  And then, we’re noticing that as studies and as agents become a little bit more complicated, as certain toxicities require a little bit more overnight observation, we’ve built the capacity to have patients stay overnight and be monitored, to monitor for cytokine release syndrome and even having telemetry monitoring is something that we’ve build capacity around.  But one of the more exciting elements and developments, as I’m sure you are also excited about, is the development of cell therapies.  

As you mentioned briefly, when we discussed Peter Mac at the beginning, we have quite a large CAR T sensor here, a cell therapy centre, where we’ve been able to develop our own CAR T agents but also, conduct studies of our sponsors.  And having patients stay for days to be monitored and having a dedicated intensive care unit for the cases of bad CRS has been something that’s been really valuable in allowing us to do these studies.

Julie Gargano: Thank you, Ben.  Amy, perhaps you might share some of your thoughts on this as well.

Dr Amy Prawira: Yeah.  I think, especially in recent years, early drug development, I find have taken quite a significant shift in that increasingly our agents are not […] developed, like we used to develop chemotherapy, where increasing toxicity equals increasing activity.  But our novel agents are not the same anymore.  What we find with our clinical trials, the designs have evolved significantly, where we need to take into account what the […] toxicities are, which sometimes there aren’t a lot of, and refine the design so that the drug can move forward quicker.  And in our centre, we are involved, as Ben’s centre are, in a number of different molecules.  Some of them remain chemotherapy-based in combination or novel delivery systems.  Immuno-oncology, for sure, targeted agents.  

Because at the Kinghorn, we’re affiliated with the Garvan Institute.  In fact, the Kinghorn is a joint facility of St Vincent’s and Garvan Institute, so we have one of the largest genomic sequencing facilities that is available, so that we can try to match patients through genomically matched clinical trials.  But yes, I think that’s probably been the most significant shift.  Sometimes accelerated titration design or intrapatient dose escalation and increasing inclusivity of patients with comorbidities, such as HIV or even […] autoimmune diseases, I think that’s probably been the shift that we can see.

Julie Gargano: Thank you, yeah, definitely the complexity of studies over recent years has just increased significantly.  We’re no longer looking at drug A versus drug B.  We’re looking at these adaptive designs, accelerated titration, inter-patient, dose escalation, clinical trials, which does take quite a while to get around and fully understand, but very much seems to be the accepted way of moving forward.

Dr Amy Prawira: That’s what makes the design models. 

Question: Professor Lee, from South Korea, the developments that you’re seeing, new therapies, any specific areas of excitement that Samsung’s participating in?

Prof. Lee Jee Yun: I think the next challenge in clinical trials in the oncology field would be personalised cancer vaccine; you sequence a tumour, look at the new antigen and give cell therapy based or RNA […] based therapy, so I think that’s going to be – that type of trial will be implemented only in few centres that are ready to do – or from tumour biopsing to sequencing to cancer vaccine trials, plus-minus.  And I think it’s not going go be only solely cancer vaccine, but plus or minus IOs beyond PD1, so that’s where we should be ready for in the next few years.

Julie Gargano: Thank you, Professor Lee.  And I just really had one last question that I would like to ask Helen.  

Question: With regards to running studies in our region, what would you say are the top key features that have drawn Five Prime to running trials in Asia and have your expectations been achieved?  And thoughts on the process of running the trials here.

Dr Helen Collins: I think it’s going to be the themes you’ve heard.  Number one is the quality, because in the end, that’s what’s going to determine what the next steps are; the quality, the speed, and then the close interaction with really committed investigators.  And of course, I’ll put a plug in for how helpful and how good it has been working with Novotech.  Again, one thing that hasn’t come up is, as you keep hearing, we’re a small biotech and in a competitive area of South San Francisco, so we have staff that come and go.  And I will give the example, that we lost our regulatory person, and we also had that same flexibility and quality in working with you, where you have the people that then step in and help us out, so again, we seem not to miss a beat.  And certainly, working with larger CROs, that would be something that would be a big scope of work change, months to fill in gaps, etcetera.  A little bit off the topic, but again, it’s really back to the quality and the speed and then the feedback and the close interaction with investigators.

Julie Gargano: Thank you, Helen.  I really just wanted to take the time to thank all of our panellists.  Really appreciate you taking the time out of your busy schedule.  We’ve had such an interactive and informative session, so thank you.  And I’d like to pass back to Arsalan.

Arsalan Arif: Thank you, Julie.  And thank you to Novotech for bringing this discussion to Endpoints News.  You really had a great panel today.  I really enjoyed this discussion.  Let’s hear it one more time, let’s hear it for Dr Helen Collins, Dr Amy Prawira, Dr Ben Tran and Professor Lee Jee Yun.  And Julie, thank you again for moderating today’s session.  I really enjoyed it.  We hope to see you at the next webinar.  And from Endpoints News, I’m Arsalan Arif and I wish everyone a great rest of their day.  Thank you very much.