Case Study: Theranostic Radiopharm Trial and Evolving FDA Expectations

A Phase 1 theranostic radiopharmaceutical study entered execution with two investigational products, an evolving FDA expectation around intensive imaging, and a sponsor that had built a strong scientific program without the operational scaffolding underneath it. Progress required site-level radiopharm expertise, structured cross-functional integration, and a willingness to push back on the sponsor when experience warranted it.

A Phase 1 theranostic radiopharmaceutical study can look like a familiar early-phase oncology trial on paper. In practice, there are multiple elements that contribute to complexity. It asks the operational team to manage made-to-order dosing per patient per visit, multiple imaging timepoints across several days, well counter calibrations, locally validated dosimetry software at the site level, and a budget model that conventional grants tools were never built to estimate.

The sponsor brought a program in advanced solid tumors to Precision under exactly those conditions, with two investigational products and evolving FDA expectations. They had built a strong scientific program but had not built the operational scaffolding underneath it, and they intentionally leaned on Precision for that expertise rather than trying to construct it from scratch.

Study Overview

Theranostic studies pair a diagnostic radiolabeled agent with a therapeutic one, which means two IPs in motion across the same patient. Each dose is made to order. Each scan has to land inside a narrow window. Both isotopes used here have slightly longer half-lives than what some radiopharm studies rely on, which helps, but it does not change the underlying operational shape of the work.

FDA comments shifted the work further. There was an increase in blood and urine dosimetry sampling timepoints for each participant resulting in up to 7 samples of each within an ~8-hour period on the day of receiving the imaging IP for the first time and also on the day of receiving the therapeutic IP for the first time. The development of a detailed Dosimetry Analysis Plan that also had to be submitted to the FDA. Then, for dose expansion, an additional dose level lower than planned starting dose level was added.

In addition, the intensive imaging cohort, originally framed at around five patients, was expanded to twenty under FDA feedback that came in during the initial IND period. Sites without that capability still participate, but only outside the intensive imaging cohort. That kind of mid-startup expectation shift puts pressure on site selection, site prioritization, scheduling, and per-patient cost projection at the same time. If a site had fast startup but couldn’t accommodate intensive imaging then they wouldn’t be able to help us get to first-patient-in and through that first dose level.

Underneath the science was a sponsor that was new to running radiopharm operations at this scale. The program had two INDs, comments from FDA on both, and three protocol versions before the first SIV. That is the kind of environment where an operating model has to absorb change without losing forward motion.

Strategic Focus for Theranostic Radiopharmaceutical Execution

The operating posture had to start with what radiopharm actually requires at site level. Not every site that expresses interest in a study like this is equipped to run it. Site capability turns on imaging equipment, scanner availability, RAM licensure, well counter calibration, and in some cases local availability of validated dosimetry software. Some of that can be solved with vendor support. Some of it cannot.

Precision's historical startup timelines do not separate radiopharm from other early-phase work, which means the available baseline understates how long activation actually takes. The working assumption is four weeks longer than the historical average for this type of study. That difference reflects operational experience built up across the program.

Protocol revision drove three startup cycles

The initial IND period produced FDA comments on both INDs at different times, which led to three protocol versions before the first SIV and we are gearing up for protocol version 6. We implemented three protocol amendments on top of those that occurred before the first SIV. Each one added scope. The mechanism that made the faster amendment possible was a functional impact analysis: each functional lead reviews the draft from their perspective, the team aligns internally, and the sponsor receives a consolidated read rather than a series of disconnected questions.

The sponsor expanded Precision's scope on a later amendment to include reviewing the draft protocol before finalization. That is not a routine ask. It reflects what happens when a sponsor sees that the operational team is catching issues that would otherwise become bottlenecks in execution.

Site capability and dosimetry defined feasibility

Well counters, dose calibrators, and scanners at sites had to be calibrated for each isotope by the imaging and dosimetry vendor, with annual recalibration built into the operating model. One dose level required rapid dosimetry performed locally, which meant the site needed its own validated dosimetry software. Only a small number of sites could meet that bar. Sites that could not perform local rapid dosimetry would have been excluded from participating at that dose level at all.

Having a good site mix is key. At Precision, we work with large academic centers and we have community-based health systems participating. We have independent specialized theranostic research centers as well. Using a combination gives our trials the right balance of well-oiled machines and smaller, less-recognizable but eager sites to mitigate the pain points of competing for the same patient population or resources and operational bottlenecks or silos that can come along with larger sites. Instead, as long as a site has the pieces of the puzzle, we can help them put it together specific to our study. And in doing so, we get the bonus byproduct of establishing strong relationships with the site staff early on.

Per-patient cost projection became its own workstream. Most of the imaging on this study is invoiceable because the specific modalities and frequency of imaging required. In addition, the imaging performed respective to the imaging IP is purely research related (i.e. scans performed to get images to see if the specific tumor had uptake of the imaging IP are essentially investigational scans).The grants tooling used to project per-patient cost was not built to absorb that variability, so the team built a side tool with contracts to reconcile actuals against projections. The grants budget has been advanced three to four times since the first patient enrolled in September. Site budget negotiations also run longer than typical because more departments at each site need to be involved in the coverage analysis.

Incorporation of checkpoints as safeguards ensuring responsible stewardship of resources

These trials are expensive. Each made-to-order dose and the just in time delivery has a high cost. For sites, these trials require a ton of interdepartmental coordination, large number of staff members, time-consuming orchestration and scheduling. Plus, to help prevent unintentional financial burden a patient may incur due to the very long visits (including those that occur over several consecutive days), the sponsor is often providing reimbursement for patient travel/meals. Responsible stewardship of resources and checkpoints help keep those costs transparent and under control.

Lab and clinical integration removed the sponsor coordination load

The lab PM joins clinical meetings and the clinical PM joins lab bi-weeklies. A standing weekly informal touch base sits on top of that. The structural point of the design is that the sponsor does not have to act as the go-between when something surfaces in one workstream that affects the other.

The IRT carries weight in this model. Two radiolabeled IPs moving across sites and patients cannot be managed manually. Early IRT safeguards were too tight and required tickets to resolve, and the specifications have been updated through structured iteration. The IRT system was integral for managing the workflow between Precision for Medicine and the Sponsor’s drug supply chain. A well-developed system is foundational to making the rest of the operating model hold.

From Bid to Operating Model

The bid was awarded within twenty-four hours of the defense. What the sponsor responded to was a team that had radiopharm coordinator experience at site level, a conversational bid posture, and a willingness to pivot mid-bid when the team recognized they were spending time on content the sponsor did not need to hear. That posture has continued into execution.

The mid-sized CRO footprint has been part of the fit. The functional breadth is wide enough that critical capability stays in-house. The structure is also small enough that workstreams do not operate in silos. That balance is hard to specify in a bid and easier to recognize once a sponsor is working with the team.

Several lessons stand out from this engagement:

1. Radiopharm is an operational category, not a therapeutic area: Staffing, site selection, and timeline assumptions all need to reflect that. Generalist early-phase experience does not interchange with radiopharm experience.

2. Site capability has to be assessed at the equipment and software level: A variety of activities from scanner availability, scanner calibration, and RAM licensure to dose calibration, well counter calibration, and validated dosimetry software determine which sites can actually participate at which dose levels.

3. Site resourcing is a critical consideration. Sites require substantial support and CRA allocations should be managed with this in mind.

4. Standing cross-functional touch bases reduce sponsor coordination load: Lab and clinical alignment should not require the sponsor as intermediary, particularly on studies where both workstreams move at the same pace.

5. Transparency about internal mistakes builds trust faster than silent fixes while pairing it with mutual accountability sets us apart: The foundation of our high-performing project team is a culture of transparency and mutual accountability, fostering trust, alignment, and success. Surfacing issues with the fix and alternatives in hand reinforces the working relationship rather than weakening it.

6. Protocol amendment velocity is a real differentiator: A structured functional impact analysis turns amendment review from a sequential burden into a parallel one.

Running Complex Theranostic Radiopharmaceutical Trials

Theranostic radiopharmaceutical programs rarely break down at a single point. They expose whether the operating model can absorb regulatory change, site capability variability, and supply chain complexity at the same time. This study shows what it takes to keep moving in that environment: site-level expertise, structured cross-functional integration, and a sponsor relationship built on direct communication about what is working and what is not.

At Precision, this is the kind of execution challenge that benefits from radiopharm experience at the coordinator level, not only at the leadership level. When studies require validated dosimetry, calibrated well counters, evolving imaging cohorts, and made-to-order dosing per visit, building an operating model that can hold under real conditions comes first.