Biomarker-driven oncology trials are advancing precision medicine, but they also introduce significant operational and regulatory complexity. In this video interview, Brant Nicks, ACE (Allucent Center of Expertise) Therapeutic Strategy Head of Oncology and Hematology at Allucent, shares frontline insights on what it takes to execute these studies successfully, from early-phase dose optimization through long-term safety follow-up.
Nicks explains how biomarker-gated trials further narrow already small patient populations, driving high screen failure rates and increasing site burden. He discusses why assay development, companion diagnostic development and realistic enrollment planning are critical to mitigating these challenges, and how tumor boards, along with improved molecular matching, are helping sponsors address recruitment barriers.
The conversation also explores evolving regulatory expectations, including fit-for-purpose assay validation, extended safety follow-up and the impact of initiatives like Project Optimus on dose optimization. Looking ahead, Nicks addresses how precision oncology innovations such as CAR-T and other cell therapies can balance faster access with the need for robust long-term safety data, while expanding patient access without compromising long-term safety oversight.
Stephanie Butler:
Welcome everyone. I am Stephanie Butler with Fierce Biotech, and I'm delighted to be joined here today by Brant Nicks, ACE Therapeutic Strategy Head Oncology and Hematology at Allucent. We're here today for a really timely discussion on the operational, regulatory and clinical reality shaping biomarker-driven oncology trials and what it will take to scale precision medicine safely and effectively. But before we begin, I'd love to just get a little background on you, Brant and Allucent, So welcome.
Brant Nicks:
Great. Stephanie, thank you for having me. I certainly appreciate it. It's very nice to be here. From my background perspective, I've been in the industry for some time since 1996, predominantly with larger CROs. I've worked as a monitor up through in project management as well as associate director on the CRO side for delivery. I also have some experience working on the sponsor side, working in small mid-biotech. And most recently I worked for central IRB.
So I have some well-rounded experience, but I'm happy to be at Allucent, which is a small to mid-CRO rather, which is geared at supporting small to mid-biotech for exactly this phase of research, the early phase hem-onc research, dose escalation, dose binding predominantly in really taking compounds forward from bench to clinic. So again, great to be here and I look forward to the discussion.
Stephanie Butler:
Perfect. I mean, given your background, I think you're going to have some great insights on some of these topics that we're going to bring up today.
Okay. So I want to start by asking you, what do you think are the biggest operational challenges in executing biomarker-driven oncology trials, such as things like patient recruitment, assay performance, or companion diagnostic development? And then how can the industry help to overcome them?
Brant Nicks:
So it's obviously important and we've evolved through personalized medicine to adopt biomarkers, which is these are great problems to have. We are advancing research to the point where we are working towards specialized medicine and that involves a tremendous amount of complexity that we've set ourselves up for, but it's also up to us to grapple with.
So obviously a clinical trial that is biomarker gated is looking for even a further subset of the target population. So that in itself proves that the patient recruitment will be even more challenging.
Stephanie Butler:
Right.
Brant Nicks:
And as you get into the lower incidence oncology indications, which border on the rare disease enrollment rates themselves, this further fractionates what you're looking for. So suffice to say this is a headache for industry and for sites alike. You see struggles with things like high screen failure rates when patients don't ultimately express an assay, which as much as you plan for it, it's a letdown.
I'm working on a trial currently with upwards of a 80% screen fail rate. And while, as I said, that's planned for, it's compensated, the timeline's compensated for it, from a site side, it's really challenging work to go through all of that screening effort repeatedly, not to have a patient that qualifies. And even to go through the activation process and continually look through your medical records and try and find those patients not to have a hit and a success. The sites are downtrodden, unfortunately, just going through that work.
I think that the need to overcome that is really through assay development, assay improvement. I think we'll talk a bit later about the tumor boards and really looking to make sure that we can match biomarkers, patients who are known to express the biomarkers with the appropriate clinical trial. And there's a number of methodologies that are in development and in execution for that, a number of companies that have popped up in this space that are really making giant strides in exactly that to chip away at the recruitment obstacles themselves.
I think secondary to that, and I think you mentioned it in the question itself, is companion diagnostic development. It's been a challenge for some time to, in parallel, enroll a challenging population, as well as to develop an assay while you're going through those rigors.
The good news is that there's a tremendous amount more assays that are in development. There are panels that are covered by standard of care in some regions, for example, that really help to take us a long way for the assay development itself.
And then I think all of this boils down to increased logistics and complexity for clinical trials, which has been above and beyond biomarkers. That's been growing logarithmically for the past decades. And again, these are good problems to have. We are advancing science. There are times where a secondary and exploratory objective that is put in that adds complexity, that becomes the primary objective in the follow-on trial. It really is that signaling that gets amplified and helps to support the efficacy, safety, the profile of the drug itself. So I'm not one that shies away from the complexity, but it does bear tremendous forethought and planning to be able to help ease that and to weave it into a clinical trial and have that be successful.
So yes, I think that that's where prospective planning, really being realistic about the timelines, including the enrollment, including those screen failure rates, and taking a long, valid look down the runway and trying to mitigate any of the pitfalls that are going to arise and just being upfront with both sites and regulators and ultimately patients about what's involved is the key to overcoming some of the obstacles themselves.
Stephanie Butler:
Right. I mean, it's a great point that we're advancing the science, and that's really exciting. It's great for the patients, but it brings with it some added complexities that you really need to take into consideration when you start doing this.
Brant Nicks:
Ultimately, these are good problems to have, but the day-to-day can inject some frustration of the process, unfortunately.
Stephanie Butler:
It can be a little daunting, right? There are other challenges, and some are on the regulatory side, so I want to move on to that a little bit. So what do you think are the critical regulatory expectations from the FDA or EMA for biomarker-driven trials, particularly around the assay validation, as you mentioned, or extended safety follow-up and integration with initiatives like Project Optimus?
Brant Nicks:
So these are all good things in the right direction, honestly. The follow-up, it can be a little challenging to grapple with as well, but I think Project Optimus has really made a stark difference in the way that we approach dosing itself. And I'm not sure that we felt the true impact of that at this particular time point, but it's certainly in the right place of eradicating the need to stretch things to the maximum tolerated dose and really look for that optimal dose is something that it seems so obvious in retrospect.
It was there for the taking, but we were really asking clinicians and patients to be put through some pretty extreme paces to reach that maximum dose, whereas what we're looking for is the optimal. So all of this is steps in the right direction.
So both the FDA as well as the EMA require biomarker-driven trials to have fit-for-purpose assays with validation and rigor to really dial that down. So I think at the root of your question, that is the outcome, right? That's what we're really seeking and the parameters that we're working within is the fitfor- purpose need.
From the follow-up perspective, it's variable across the type of vectors and what we're capturing. It can be anywhere from five to 15 years of complete follow-up. Sponsors need to be sure that they prepare for that prospectively, even if the trial doesn't go forward, unfortunately, if something happens and the asset is put on hold or potentially shelved, that follow-up for the patients who are exposed still needs to be covered.
So that it is an important component and CROs are developing follow-up structures to be able to help ease that and to do it efficiently so that there's less burden on both sponsors as well as patients over time.
Stephanie Butler:
That's a great point on the follow-up. I hadn't thought of that previously, but it's something you have to be willing and able to do.
Brant Nicks:
Nobody plans for that, unfortunately. When you're excited about your asset and going through the planning of it, you plan for success as you should, but there is a lot of risk in hem-onc development, so it is an outcome.
Stephanie Butler:
Yeah. So you have to take that into consideration. You mentioned the tumor board, so I do want to get into those as expected. So how are the multidisciplinary tumor boards using the molecular profiling alongside the patient comorbidities to guide those treatment decisions while also minimizing risks when biomarkers don't clearly align?
Brant Nicks:
It's absolutely central to it. So tumor boards have been around for as long as research, as long as treatment has been around for oncology, and they keep adding to what can be prognosticating. So obviously the advances in imaging and the surgical input, et cetera, their list of tools for tumor boards has been vast and growing and to add biomarkers into that is where we want to be with personalized medicine.
I think that the risk comes in when there is some uncertainty in biomarker assessments, and that's really where I think tumor boards are struggling. There are some that are very obviously cut and dry that help with shaping of the decisions, but for patient selection criteria, there are times where the tumor board struggles with how a patient may fit into a particular bucket, if you will.
Stephanie Butler:
Right.
Brant Nicks:
I think the way to overcome that is really through cautious interpretation of the biomarker and the matching outcomes, and then it takes continuous reassessment. So I know that there are tumor boards at learning institutions who have real-time updates, flagging of eligible patients, and make sure that all their clinical trials are properly mapped and active when a cohort may be open to make sure that the tumor board has the most accessible information.
There's also some recent news. The FDA put out a posting just this week about some advances that they're looking at for real-time data and review, which I think has the potential to impact both tumor boards and decision-makings. The announcement is predicated around support of faster approvals and faster review timelines, but there may be some of the technology in the pipeline, and the monitoring, that can help tumor boards as well.
So it's obviously a “watch this space”, as it’s fairly premature to be able to flip a switch and say that this is going to have an impact downstream on tumor boards. But the potential in the lead from the agency is really encouraging for research, which has needed some overhaul for some time.
Stephanie Butler:
No. That's interesting. I hadn't seen that. So that's definitely something to watch going forward.
Brant Nicks:
It's a significant announcement. It's paired with industry, with MD Anderson, with a few other academic sites, and then a tech company who's helping to drive real-time data to the agency for adjudication and review.
Stephanie Butler:
Yeah. Makes sense. Great insights there on how we can handle some of those issues and deal, especially with the tumor boards. As we kind of talk about some of the newer technologies, I want to get into as the newer precision oncology approaches, with new precision oncology approaches such as the in vivo cell therapies, as they move toward a broader clinical use, how do you see the field balancing wider access and faster treatment timelines with the need for a robust long-term safety data?
Brant Nicks:
It's tough. And here, again, I sound like a broken record, but I mean, these are great problems to have. CAR T is obviously reshaping treatment modalities, particularly on the hematology side, but in solid tumors as well.
The problem is, again, the complexity and the ability to be able to package CAR T for community settings, for example, and really take CAR T downstream outside of the academic medical centers and to ultimately look at the expense of CAR T as well. But I think precision-driven approaches, long-term studies track risk, they track secondary malignancies, dysregulation. And I think with adaptive trial designs, they help to evolve with that data.
So the metrics that are available, really being able to evaluate therapies holistically and combining what's known from a long-term, as well as inputting what's happening in a real-time, shorter-term efficacy setting is helpful to be able to evaluate exactly that.
And then I know from a regulatory perspective, there is acceptance from both the FDA and EMA to really help with the data collection milestones and that harmonization. So as things are expanding and there are more options on a global level, we need to think about how to really get that to the patients in need. And this is where proper site selection, really proper looking at incidence prevalence epidemiology and the geography of where need may be, and matching that with the site selection for clinical trials, is the key to bringing things to patients, and CROs like Allucent are very adept at the feasibility process to be able to help match and overcome some of those imbalances.
So again, good problems to have, a number of considerations and the complexity is something that over time we'll continue to chip away at. But for now, some of the immunotherapies, CAR T and then radioligands are going to be limited to your larger academic institution.
Stephanie Butler:
Which makes sense. I mean, this has been a fantastic conversation. I mean, some excellent points. There's so much potential here, but definitely some risks and some things you need to work through. So it's great to have folks like you who are looking into all of those and can help people with those as they get into the space and try to ultimately do what we all want to do, which is help the patients.
So thank you so much, Brant. Thank you so much to Allucent for such an engaging discussion. I am looking forward to seeing how this develops down the road, so definitely keep me posted.
Brant Nicks:
I think we're all interested to see how they develop down the road. And I agree with you, there are risks, but the downside in not overcoming this risk is too large. We're advancing science, we're advancing therapies, and we're changing survival curves, so for the better, by the way. So again, this is a really exciting time to be in hem-onc research. So thank you for your time. Thank you for letting me share my thoughts.