The Fortrea Podcast
The Fortrea Podcast
Radiopharmaceuticals Trials: An Operational Playbook | Ep 1 | Why Radiopharmaceuticals?
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Radiopharmaceuticals are generating significant excitement across oncology, offering a highly targeted approach that combines precision medicine with the power of radiation. In this opening episode of Radiopharmaceutical Trials: An Operational Playbook, the discussion explores why these therapies are attracting growing attention from sponsors, researchers, clinicians, and investors alike, and what is driving their rapid momentum across the drug development landscape.
Host Hector Herrero is joined by Dr. Kavi Karra and Dr. Paulo Nunes to examine both the scientific promise and the operational realities of radiopharmaceutical development. Together, they discuss how radiopharmaceutical trials differ from traditional oncology studies, from specialized site requirements and radiation safety considerations to the complex coordination needed across clinical, manufacturing, and logistics teams.
Host: Hector Herrero, Senior Director on Global Project Management at Fortrea
Participants: Dr. Kavi Karra, Senior Medical Director GE HealthCare and Dr. Paulo Nunes, Medical Director at Fortrea
Radiopharmaceuticals are one of those topics that seems to be everywhere right now in oncology. You hear about them at conferences, you see them in pipelines, you read headlines about breakthroughs, and yet and yet, when you scratch beneath the surface, a lot of people still aren't quite sure what makes them so different. And that's not really a surprise because radiopharmaceuticals don't just change how we treat the cancer, but they also change how we run clinical trials. So behind every promising result, there's a complex operational machine, specialized sites, radiation safety requirements, very, very, very tight timelines, and coordination across teams that don't always work together in traditional oncology. My name is Hector Aurero, I'm Senior Director on Global Program Management at Fortria, and this is Radiopharmaceutical Trials, the Playbook. In this first episode, we will talk about why radiopharmaceuticals are gaining so much momentum, how their trials differ from traditional oncology studies, and why the behind-the-scenes operations really matter. Today I'm very happy to be joined by Dr. Ravi Kara and Dr. Paolo Nunis. Great to have you both here.
SPEAKER_02I lead the oncology medical team at uh GE Healthcare. Very glad to be a part of this uh podcast.
SPEAKER_01And I am Paolo Nunis. I am a medical oncologist and one of the for three years medical directors. Here at the company, I work with radio pharmaceutical projects, uh, both in the therapeutic and diagnostic spaces, and I'm happy to join this podcast series. Thank you.
SPEAKER_00So radio pharmaceuticals have existed for many years, but it feels like something has shifted. There's a really growing interest in targeted radiotherapies. So, Dr. Kara, from your perspective, what's driving this momentum?
SPEAKER_02Well, uh, radiopharmaceuticals have uh existed for almost a century now. Uh radioactive iodin has been used to treat uh thyroid disorders, including thyroid cancers. Now, radiopharmaceuticals have undergone multiple uh niders and zeniths in the intervening decades. The fact is uh currently we are at a pivotal moment for the use of radiopharmaceuticals in oncology, both diagnostic and theragnostic. Uh the Port Montreal word theragnostics uh actually describes the integration of uh targeted therapeutic with an analog diagnostic. This theragnostics has uh actually kick-started the renaissance of uh radiopharmaceuticals with uh a remarkable increase in clinical trials, leading to multiple uh regulatory approvals, which have ensured radiopharmaceutical therapies are integrated into uh oncology treatment options across uh several solid tumor types. Now, there are several reports that uh indicate uh radiopharmaceutical market is growing by leaps and bounds, uh, leading to a total market uh share of oil, which is going to be in double digits uh in billions by 2030 and beyond. Three main drivers for all of this growth that we are currently observing. Number one is uh the array of uh biological targets for radio pharmaceuticals have increased phenomenally from um prostate-specific membrane antigen to sometostate in uh receptor type 2, fibroblast activation protein, and the list goes on. Number two, uh the industrial scale radioisotope production, stable and robust chelator conjugate systems, and to a certain extent, uh the ability to transport the products across countries. And number three is uh increasing disease indications, earlier line and early stage disease, and uh the possibility to uh combine radiopharmaceuticals with the other therapies. Now, these are the three key drivers from my perspective that are uh driving the current momentum.
SPEAKER_00Also, I think that one item which really resonates with people is the idea of precision. So delivering radiation exactly where it is needed rather than broadly across healthy tissue. So, Paulo, from your point of view, we are also seeing um a much broader pipeline, especially across solid tumors. How do you see sponsors thinking about radio pharmaceuticals today?
SPEAKER_01Connecting with what Dr. Kaher just mentioned, uh, I think uh what we see today is the result of this successful story, especially in the theranoustic space, right? So for many years, what radio pharmaceuticals were mainly used as a diagnostic tool. So we had all the development of FDG PET scans, uh and many other nuclear medicine tracers. But I I must say that like um a real groundbreaking moment was the advent of PSMA-based therapies, right? That really put the tyrannostic concept at the spotlight, and now we've seen like uh real nice and differently good development in real ligand therapies. Like now you're exploring different types of radiation, right? Alpha beta therapies. Uh, we have exploring different uh tracers, uh, so not only peptide-based as used in neuroendoctrin tumors or prostate cancer, but now antibodies, uh, and many other things, different linkers. So it's it's uh uh you know a whole new world in oncology drug development. And of course, we have many studies that are in the early phase moment, but things are moving now to registrational studies. And as Ravi mentioned before, uh by 2030 or around that date, we will have all these new drugs in the market.
SPEAKER_00Yeah, what they what is really interesting to me as well is that radio pharmaceuticals are not just one thing. So they are not just drugs, they are not just radiation. They really combine a pharmaceutical targeting mechanism with radiation delivery, and you know, that makes this uh really uh uh something powerful. But of course, that also introduces uh some complexity and make things a little bit more complicated. And that complexity really starts to show once you move into the clinical trials, even more than with any other any other study. One thing I I often hear from teams when they are really new to this space of radio ligand therapies or radiopharmaceuticals, however you we want to call it, is that well, we didn't realize how different this was going to be. Yeah, there are some relevant differences uh which we are going to be discussing. Um, let's start talking about some of them. First of all, is probably the most important one from my perspective, which is the question about the site capabilities and the ability at site level of working all together. So these trials often require uh nuclear medicine departments, radio pharmacy, radiation training staff, plus the oncologies, plus uh, you know, uh hopefully all of those things uh very close, uh specific storage um and handling procedures, things that are not so standard at every oncology side. Um, Paulo, where do you see the the biggest gaps when when trials are being set up from your perspective and also from your experience at the side?
SPEAKER_01I think that's a very important question, especially when we are planning a clinical trial. I think what one of the main challenges is the teamwork that is needed for uh radiopharmaceutical trials. So you need like a very well team that connected across different departments, so nuclear medicine, oncology, radiology, pathology. So I think that creates an extra layer of complexity in terms of site stuff. And also something that I think it's important is the training. So, especially for oncology nurses and study coordinators, they might not be familiar with the different concepts of radio pharmaceuticals and how that applies to clinical trials. And very important is the site being prepared to receive those trials.
SPEAKER_00So, even when all these uh all the right infrastructure exists, there are often also some extra layers, for example, regulatory and radiation specific oversight. Uh, Cavi, from also from your perspective, how does this change the way uh from your perspective, uh how these things change the approach and how the trials are planned?
SPEAKER_02Given the complexity of the treatments and uh the inherent bio and radiation hazard to patients, caregivers, and healthcare personnel, uh, there are obvious safeguards that are in place. Now, this uh translates to the obvious additional regulatory and other oversight frameworks on top of uh the usual clinical trial frameworks. There are four major ones. Uh, number one would be the national radiation protection rules, which are country specific, and every clinical trial protocol needs to adhere to that. Uh, the radio pharmaceutical uh quality control from production to infusion, uh, which is uh quite uh, let's say at a completely different level and has to be done on the site. Uh, and then uh comes the imaging standardization, whether validation of your uh scanners, whether it's BET CD, spec CD, or other software to ensure uh data consistency across uh uh multiple centers when you're running a multi-centric trial. And of course, when it comes to diagnostics, uh the companion diagnostics, they have to comply with uh in vitro diagnostic regulation, which is a bit different from the usual clinical trial regulation for drugs. Uh, all of this actually leads to uh a longer starter, longer recruitment and follow-up, which eventually adds to an overall study duration. But uh despite uh all these challenges, uh, what really happens is that the amount of work that needs to go in to have a solid startup means, and also continuation means that as of now, it's primarily the tertiary care centers that are engaging in clinical trials with radio pharmaceuticals. Now, um to reach one level below, well, there needs to be some industrial level frameworks that need to be established. More and more sites, not just the tertiary ones, but uh the level three and level two sites need to get uh used to how to work uh with the radio pharmaceuticals, provided there is uh adequate infrastructure as well. So, yes, there are some uh complexities and challenges, but I'm sure that uh we will get there at one point in time.
SPEAKER_00Yeah, and and and something very relevant, very much connected with everything we have just said, is that there is one thing we cannot forget about, which is how all these situations are impacting the patient journey. At the end of the day, we have a patient here who is going to be treated, who is in a under a severe condition like cancer. And at the end of the day, all these situations are going to impact them. So scheduling a visit is just not about, in these cases, clinic availability. It's about isotope production, delivery windows, staff availability, safety procedures, all have to be lined up perfectly. Um, so compared with traditional oncology trials, patient flow and treatment administration become much more tightly choreographed in these cases. And uh well, this brings us to what I think is also one of the most underappreciated aspects of radio ligand therapy trials, which is operations. If you know about these kind of studies, yeah, you realize how important operations are here. If you are not, uh this could be a surprise for some of you, for some of the people listening to us today. Many of these therapies involve short half-life radioactive materials. In very simple terms, time is not our friend here. If something slips, you just don't delete the treatment. You may lose that dose entirely, and of course, that will go back to the patient, because the patient will not be treated that day, right? And you can imagine all the issues that this may uh came with. So, uh, Dr. Kara, in your in your opinion, can you explain why, from your perspective, uh again, uh logistics are so critical here in this kind of studies?
SPEAKER_02Uh well, radiopharmaceutical trials are uh a very unique group in that they are operationally one of the heaviest, uh not just from a site perspective, but for all the stakeholders involved. Just looking at uh the site perspective, uh, right from uh isotope and drug protection and distribution, as you mentioned before, the short half-life of radionuclides. This actually precludes uh what you call as the off-the-shelf concept. And uh the production actually starts when you have a patient ready. Sometimes there is a quality control issue, and uh that quality control failure leads to an unreated patient patient under lost opportunity, and vice versa. What we also need to understand is the additional burden that uh diagnostics are actually not providing any real-time benefit to the patient in contrast to theragnostics. So there is an additional uh burden there with respect to patients getting enrolled in uh uh purely diagnostic trials. So we need to urgently scale up industrial level RPT or radio pharmaceutical production, storage, cold chain supply, uh all of that. But the key is uh, from my perspective, coordination is needed at the highest level for all stakeholders involved, sites, sponsors, CRM personnel, and not just at uh the start of the trial, but for each patient at each site. Because without that kind of a very close laser-focused coordination, uh it's going to be very difficult to run a smooth radio pharmaceutical trial.
SPEAKER_00And that's what's happening also behind the scene, right? That it is uh you know really a chain of dependencies, what we cannot see, right? But is they are really so important. So all these isotope manufacturers, radio pharmacists, uh couriers, uh teams, all of them working behind the scene to ensure that you know the patients can really receive on time um the treatments. Uh Paulo, uh what what happens when when one what when one link in that chain breaks? And and here I think it is very interesting to also hear from your experience at sites.
SPEAKER_01It all impacts the the the feeling from the site and the patients, right? So for instance, as uh Ravi just mentioned, I missed uh infusion opportunity because there was an issue with the QC or the drug didn't was ship was not shipped on time. You know, the the patient will get you know frustrated because you know he's willing to participate sometimes in a study that won't have a direct benefit, and he scheduled his life, you know, uh meetings, appointments, kids to participate in the study, and then on the last minute the infusion was cancelled. The site staff will also be impacted by all those issues that are outside of their control, right? Uh so study coordinators, study nurses, investigators. So I I think uh connecting with what Ravi just mentioned, you know, I I think the main impact not only in terms of the project timeline and uh costs that of course are impacted, but on the overall morale of the trial, right? People will get frustrated, angry, and in the end will impact you know the overall willingness to participate in the study. So I think for me that's the most important impact from any break in that chain, right? Uh timelines, budget, you can always kind of play around, but the emotional consequences of that chain, especially for patients, right? That's something that you cannot easily uh solve.
SPEAKER_00Yeah, and that's why uh well people who are usually working on this space, we used to say that uh well, radio pharmaceutical innovation is not only scientific, it's also operational. And in some cases it can become also emotional, which we need really to avoid that. So uh, well, success in all in all these cases that we have described today um uh depends on understanding the full ecosystem. It's not just only one piece, it is that all these pieces can really work together. So, what we have talked today really sets the stage for the rest of this series of podcasts. Uh, radiopharmaceuticals, radio ligand therapies offer an incredible promise, uh but realizing that promise in clinical trials require a different mindset, different preparation, and a lot of operational discipline. In the next episodes, we will go deeper into how to choose the right sides, the logistics and supply chain essentials, and common operational challenges, and how to avoid them, of course. Thank you very much, Dr. Carra. Thank you very much, uh Paolo, for this great discussion. And thanks to everyone listening. We will see you in the next episode.