Radiopharm Theranostics has received ethics approval from Australia’s Bellberry HREC to initiate a first-in-human Phase 1 study of RAD 402, an anti-KLK3 monoclonal antibody labeled with terbium-161, in patients with metastatic or locally advanced prostate cancer. The program advances a novel target–isotope combination for the category and would be among the earliest company-sponsored therapeutic trials using 161Tb. Preclinical work reported strong tumor uptake with limited bone marrow signal and a hepatic excretion profile consistent with antibody-based radiotherapeutics. Radiopharm has secured radionuclide supply from Terthera and radiolabeling support from Cyclotek to enable startup.
The core shift here is twofold: moving beyond PSMA as the dominant prostate cancer antigen and advancing 161Tb as an alternative to 177Lu. KLK3 encodes the PSA protein and is broadly expressed in prostate tissue and adenocarcinoma metastases. By using a full-length IgG1 that internalizes into prostate cells, the company is positioning 161Tb’s dual emission of beta particles and short-range Auger electrons to deliver intracellular radiation where internalization is achieved. Operationally, the Australian pathway allows rapid FIH activation under an ethics-led framework, with manufacturing and onshore radiolabeling set up to support early cohorts.
Strategically, this is an expansion play into a crowded but still evolving radiopharmaceutical market. PSMA-targeted ligands have validated the category and raised expectations on response durability, dosimetry discipline, and site readiness. A KLK3-targeted approach could open an orthogonal patient segment, including PSMA-low disease and post-PSMA progression, if tumor targeting and internalization translate clinically. The use of 161Tb is a technical bet that Auger electrons can enhance DNA damage when the payload reaches intracellular targets; that promise hinges on consistent internalization and adequate tumor residence time given antibody pharmacokinetics. The counterpressure is biology risk: PSA/KLK3 is predominantly secreted, and target accessibility for an antibody on the cell surface must be confirmed in humans to justify the mechanism.
For sites, the study adds to the growing queue of complex radiopharmaceutical protocols. Centers will need reliable 161Tb access, radiopharmacy capacity for antibody radiolabeling, and robust dosimetry and radiation safety workflows. The Cyclotek relationship may simplify Australian activation, but expansion outside the region will require additional qualified radiopharmacy partners and logistics, given 161Tb’s production footprint. CROs and sponsors should anticipate longer infusion and monitoring windows typical of antibody-based radiotherapeutics, plus added imaging, PK, and organ dose assessments common in early radionuclide trials. Regulators will focus on marrow and liver dose constraints, time–activity curves, and whether preselection by biomarker or imaging is necessary to manage risk and variability. For patients and treating physicians, the unmet need remains highest after PSMA-directed therapy, where a non-PSMA target could be relevant if on-target delivery is demonstrated.
Key near-term readouts will be classic Phase 1 signals: hematologic and hepatic dose-limiting toxicities, organ dosimetry, tumor uptake, and early activity markers such as PSA decline and radiographic response. Watch for whether the protocol layers in companion imaging or tissue confirmation to de-risk target engagement, how many cohorts are required to reach a recommended Phase 2 dose, and whether the pharmacokinetic tail of an IgG1 complicates marrow exposure. On the operational side, the durability of the 161Tb supply and the replicability of radiolabeling at scale will determine how quickly the program can move beyond Australia. The broader question is whether KLK3 biology and 161Tb’s emission profile can carve out a clinically and commercially defensible niche alongside PSMA ligands, alpha emitters, and next-generation combinations now moving through late-stage development.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
