By Deborah Borfitz 

August 21, 2025 | Radiopharmaceutical therapy (RPT) has been around for a long time now, but advances in technology and understanding of the actionable molecular pathways that drive cancer have fueled a resurgence in interest and investment in the therapeutic modality, according to Lola Fashoyin-Aje, M.D., MPH, senior vice president, head of regulatory oncology, cell and gene at Parexel. The popularity of RPTs is driven largely by theranostics combining diagnostic imaging and targeted therapy into a single, integrated system to more precisely deliver radiation to tumor cells and thereby minimize damage to healthy tissue.  

Many RPT clinical trials were underway even before the 2018 marketing approval of Lutathera (Novartis) for the treatment of a rare type of neuroendocrine tumor, marking the first time a radioactive drug was approved for this type of cancer therapy, she says. The focus has more recently turned to improving the anti-cancer precision of RPT as well as “logistical aspects” of evaluating these therapies in clinical trials.  There is increasing acknowledgment that RPTs may provide patient-centric advantages over more traditional anti-cancer therapeutic strategies. 

Fashoyin-Aje is no stranger to RPT or cancer therapies in general. Prior to joining Parexel last month, she worked at the Food and Drug Administration (FDA) for nearly 12 years—first as a primary reviewer of mostly solid tumor oncology products in the Center for Drug Evaluation and Research and later in the agency’s Center for Biologics Evaluation and Research supervising the clinical review of cellular, gene, and tissue therapy products. 

“The limited number of approved RPTs doesn’t really represent the amount of activity happening in this space for many years,” says Fashoyin-Aje. The holdup has been the historically low clinical trial success rate tied to the complexity of developing and regulating this ever-evolving class of cancer drugs.  

The FDA has not put out many documents on its current thinking specific to RPTs, other than labeling recommendations and guidance on the microdosing of diagnostic drugs in nonclinical studies. That’s because regulatory guidance is informed by “accumulated experience” across many different products and a broad understanding of the issues at hand, Fashoyin-Aje says. Given growing interest and activity around RPT products, fresh guidance may be forthcoming soon, she adds.  

Knowledge Gaps 

Review of RPTs products follows the conventional framework that seeks to ensure the right dose and patients have been identified and trials are optimized to measure treatment effects, and the resulting data is reviewed for evidence of effectiveness and the benefits relative to the risks, says Fashoyin-Aje. Those effects also need to be appropriately described for prescribers and patients so that clinical trial data can be used to make decisions at the bedside. 

But as with any type of complex therapy, RPTs necessitate greater coordination among multiple specialists “to ensure that as the development is unfolding there aren’t any delays,” she continues. “Regulators are trained in the fundamentals but always must lean in to evolving science because as soon as you learn one thing, the next thing is upon you.” 

“It may not be realistic to expect that regulators will always have a blueprint for how best to integrate new scientific and technological advances in drug development,” says Fashoyin-Aye. “In some ways, that blueprint is born out of learned experience. We’re in a place where there are still a lot of unanswered questions around RPTs,” including how to pick the dose that delivers the most efficacy but also minimizes the safety risks.  

The FDA’s Oncology Center of Excellence (OCE) launched Project Optimus in 2021 to reform the dose optimization and dose selection paradigm in oncology. But how the program’s framework is implemented in drug development may vary depending on the therapeutic modality, its toxicity profile, the patient population being treated, the drug’s mechanism of action, and if it is a one-time treatment (e.g., cellular or gene therapy) versus given indefinitely until the tumor progresses or for a short period of time after surgery, she explains. 

Broadly speaking, Project Optimus seeks to promote a “thoughtful approach to dose selection” when sponsors are designing early-phase trials to maximize the efficacy, safety, and tolerability of treatments during pivotal, late-phase trials, says Fashoyin-Aje. This grew out of the recognition that oncologic therapies have become more targeted and can be given long-term and, in some cases, indefinitely. 

The traditional approach to dose finding was to rely on assumptions arising from the short-term use of cytotoxic chemotherapy “where the goal was to get to the maximum tolerated dose and obliterate the tumor,” she says. Unfortunately, along with the effects on the tumor, patients also were subjected to significant toxicity due to damage to normal tissue. With newer therapies given more chronically, patients simply can’t tolerate that degree of toxicity over time. 

Decision-making around dose optimization in the RPT space is much the same as with other types of cancer drugs, except “theoretical risks” that might occur sometime in the future need greater consideration, as the length of clinical trials typically is insufficient to characterize these potential risks, says Fashoyin-Aje. How much radioactive material gets absorbed by different body organs, and the associated long-term toxicities, require close attention. Unfortunately, no great tools or biomarkers currently exist to test assumptions about “maximum absorbable dose” specific to the kidney, liver, or other at-risk organ.  

It’s Complicated

Global clinical trials of course may involve several regulatory agencies. Radiopharmaceuticals across the board are generally governed by the same set of rules as other types of drugs and biological products and the radiation aspect is typically handled by different bodies.  

Additionally, certain certifications and licensing are required for sites to be able to administer this kind of therapy and “that may vary by country or even state by state in the United States,” she continues. “So, there is this complex cast of considerations for being able to deliver the product safely and have all the logistical and operational support to ensure that happens.” 

On top of the regulatory licensing requirements, the upfront work also includes feasibility assessment and site selection, providing training and education on the RPT product and its proper handling, clinical trial design, and determining where patients are going to be transferred for their post-treatment recovery period and who is to provide that support and what they’ll be watching for, says Fashoyin-Aje. “There’s a lot and ... teams have to operate in a collaborative way,” much as medical and radiation oncologists already do in treating many types of cancers except here the partnership is between medical oncologists, nuclear medicine doctors, and their respective healthcare teams. 

The coordination also extends to scientists who are experts in handling RPT products, she adds. “In different institutions different specialties are leading the program, depending on the expertise at the site, and Parexel “can customize each development program based upon our knowledge and experience with all the different networks involved.” 

In terms of what sponsors are most wanting to know, it depends on their prior experience with RPTs, says Fashoyin-Aje. Those new to the space are mostly looking for help in mapping out the strategy from “getting a product to patients through clinical trials, to getting it approved and getting reimbursement for it.” 

Sponsors who have been operating in the RPT space for longer are generally looking for their trials to be conducted more efficiently and cost effectively, she says. To that end, they want to identify capable sites that can initiate studies quickly, ensure the safety of patients, and collect high-quality data.  

Parexel can be a partner in delivering patient-centric innovative medicines to patients and has a “cadre of experts to help to accomplish that goal every single day,” says Fashoyin-Aje. “We are singularly driven by the commitment to patients and bringing them the best science.”