Radiation therapy plays a central role in cancer care. In fact, it is estimated that 41% of cancer survivors can attribute their cure to a treatment that included radiation, unlocking the therapeutic power of radioactive approaches. Despite its clinical impact, radiotherapy remains a relatively cost-effective intervention, accounting for just 7.8% of total cancer care costs across the EU and UK.
Radioligand therapies (RLT) combine radioactive isotopes with targeted compounds, killing cancer cells while minimizing damage to surrounding healthy tissue. The already demonstrated efficacy, precision targeting and broad applicability in multiple cancer types, makes radiotherapeutics an increasingly attractive therapeutic area for developers and investors.
Yet the path to approval remains complex, especially in oncology. While 13.8% of drug development programs across all indications reach the market, the figure drops in oncology to just 3.4%. For radiopharmaceutical, success rates are not yet well studied, but the limited number of approvals in recent years speaks for itself.
These figures reflect the reality that even promising science can struggle without the right development strategy. Turning potential into progress requires careful planning. From time-sensitive logistics to fragmented hospital teams and layered regulatory frameworks, RLT trials come with challenges that can easily derail timelines if not anticipated early.
In this article, we draw on our experience as a clinical CRO specialized in oncology to outline key considerations for de-risking your RLT clinical trial. We focus on protocol design and sites selection, two of the most critical factors in setting your study up for success.
1. Designing Trials Around the Therapeutic Reality
RLT trials often face a set of unique challenges. If not addressed early in the design stage, these can lead to significant delays or avoidable protocol amendments. Below are some of the most common pitfalls we’ve encountered:
- Overly ambitious protocols
Many RLT clinical trials are designed with extensive primary and secondary objectives, dense imaging schedules, and demanding sampling plans. While well intentioned, this complexity overburdens investigators and patients (particularly in late-line settings), leading to slower enrollment, higher dropout rates, and execution challenges at site level.
This concern is echoed in the updated ICH E6(R3) guidance (point 7.4), which states that “the sponsor should not place unnecessary burden on participants and investigators.”
Tip: Clear, patient-facing materials improve enrollment. Fear of radiation can slow recruitment, so materials must explain what patients can expect and why safety protocols exist, helping address concerns before they become a barrier.
- Poor indication strategy
Radioligand therapy has shown the most consistent success in thyroid cancer, neuroendocrine tumors, and advanced prostatic cancer, where targeting is well established. Some sponsors pursue broader solid tumor indications without a strong clinical or biological rationale. A focused indication strategy, or a basket study design when appropriate, can improve feasibility and align better with regulatory expectations.
- Underuse or late integration of biomarkers
Companion diagnostics and biomarker-based inclusion criteria (such as PSMA or SSTR2 expression) are essential to patient selection in radiopharmaceutical trials. Evidence shows that biomarker-guided programs have a significantly higher success rate, improving from 1.6% to 10.7% in some analyses. This should be considered early in the design process.
–> Logistics and regulatory planning also play a critical role in radiopharmaceutical trial success. Factors such as isotope supply, QP release, and country-specific radiation approvals require careful coordination. These topics are complex and could easily be the focus of a separate article. If this is of interest, please get in touch with our team.
How to make it work: As you begin planning your study, lean into the experience and expertise of your CRO. At Pivotal, we support sponsors during the protocol development stage to ensure that trials are not only scientifically robust and sound but also operationally realistic. This includes early input on endpoints, feasibility considerations, and regulatory planning to help trials run smoothly from the start.
2. Selecting Truly Radiopharmaceutical-Ready Sites
Choosing the right sites is one of the most critical decisions in any radiopharmaceutical trial. Yet poor site selection remains one of the most common causes of delay or failure. With this in mind, let’s look at what makes a site radiotherapeutics-ready and the key factors to consider during selection.
- Not all oncology sites are radiopharmaceutical-ready
Sites must have prior experience with radiopharmaceutical or radiotherapeutic trials, as well as access to essential infrastructure. This includes experienced nuclear medicine departments equipped with SPECT or PET scanners, on-site or partnered radiopharmacies, radiation handling licenses, and a reliable isotope supply chain. Sites that may be strong in imaging or standard oncology studies often lack radioligand administration experience, and may require additional training, documentation support, or dry runs to ensure compliance.
- Poor internal coordination creates delays
A common operational bottleneck is the lack of communication between nuclear medicine, oncology, and pharmacy teams. In many hospitals, these departments operate independently, causing slow protocol implementation, unclear division of responsibilities, and delays in dose preparation, imaging scheduling, or adverse event follow-up. Strong internal coordination is essential for radiopharmaceutical trials to run smoothly.
- Responsiveness matters more than reputation
Radioligands are highly time-sensitive. Sites must be responsive and well organized, not only for scheduling doses and scans but also for managing logistics and follow-up. A site may have the right infrastructure, but if its internal processes are slow or fragmented, the trial will suffer.
How to make it work: At Pivotal, we place strong emphasis on qualifying sites that are not just technically capable, but operationally reliable. We design tailored feasibility questionnaires that assess each site’s experience with radiolabeled drugs, technical capacity, regulatory readiness, operational infrastructure, and staff training. Importantly, our Study Start-up & Regulatory team sends these questionnaires to all relevant departments, not just the oncology team, to ensure a full picture of the site’s ability to support the implementation of a RLT clinical trial.
Tip: Site dry runs prevent avoidable delays. Especially when short half-life isotopes are involved, dry runs help align departments, confirm workflows, and reduce the risk of missed first-doses.
Conclusions
Radioligand therapies hold immense promise in oncology, offering precision targeting with meaningful clinical outcomes. Delivering on that promise requires more than a strong scientific foundation, and early planning across operational and regulatory demands is essential to succeed.
In this article, we’ve focused on trial planning and site readiness, two areas that can make or break a study. Just as critical, though, is the oversight of manufacturing, isotope supply, and QP release. The earlier these elements are addressed, the smoother your trial will run, and the sooner patients will benefit from your therapy.
From protocol design to site selection and trial startup, we continue to support biotech sponsors through the nuances of radiolabeled drug development across Europe and globally. Our specialized oncology teams and deep experience in RLT help anticipate challenges before they arise. If you’re planning a radiopharmaceutical program and want to avoid common pitfalls, reach out to our team to explore a tailored feasibility strategy.
MEDIA CONTACT
Ms. Natalia Farr
