Radiopharm Theranostics has dosed the first patient in its first-in-human Phase 1 trial of RAD 402 in advanced prostate cancer, with an initial look at safety, dosimetry, and biodistribution from the first two dose levels targeted for the second half of 2026. Preclinical xenograft data showed strong tumor uptake with minimal bone and marrow signal and a hepatic clearance profile consistent with antibody-based agents.
The study (NCT07259213) is a dose-escalation trial evaluating safety, tolerability, whole-body distribution, and preliminary activity of RAD 402, a KLK3-targeted monoclonal antibody radiolabeled with terbium-161. The design aims to establish an MTD and/or RP2D before expansion. As with most radiotherapeutic first-in-human programs, the early focus is on patient-level dosimetry, hematologic tolerability, and organ exposure, alongside signal-finding on PSA kinetics and imaging.
Strategically, this is a calculated move into a crowded but still fluid prostate radiopharmaceutical landscape. Rather than chasing the increasingly saturated PSMA-ligand path, Radiopharm is testing KLK3 (the gene encoding PSA) as a tumor-localizing handle using an antibody backbone and a non-lutetium isotope. The choice of terbium-161 is notable given its beta emissions and associated short-range electron components that could augment microlesion killing and enable practical theranostic readouts. If the preclinical observation of limited marrow uptake translates clinically, the program could sidestep one of the key operational constraints for late-line patients who arrive with compromised reserve after chemotherapy and prior radioligand exposure. The flip side is biological risk: KLK3/PSA is a secreted protein, and consistent tumor retention sufficient for therapeutic indices remains to be proven in humans, especially relative to the well-validated membrane target PSMA.
The operational implications are immediate for sites and CROs. Tb-161 supply and on-time radiolabeling demand a more bespoke chain than Lu-177, and Radiopharm’s partnerships with isotope and radiochemistry providers are essential to keep screening-to-dosing windows predictable. Sites will need SPECT-capable imaging and dosimetry workflow readiness, along with radiation safety protocols adapted to an antibody’s longer circulation time. Sponsors and vendors should also note the potential shift in patient selection: if KLK3 expression or a companion imaging readout becomes an inclusion requirement, screening logistics could diverge from the established PSMA PET pathway. For regulators, the key comparators will be hematologic safety, critical organ doses, and early signs of target engagement in patients who have exhausted PSMA-directed options or who present with PSMA-low disease.
Near term, the readouts to watch in 2H 2026 are dose-dependent marrow and hepatic exposure, any early PSA or imaging concordance suggesting on-target effects, and the practical cadence of manufacturing and delivery across sites. Unresolved questions include how reliably KLK3 targeting will translate into intra-tumoral retention in metastatic settings, whether hepatic clearance introduces trade-offs for patients with liver involvement, and how scalable Tb-161 production will be if the program advances. If initial data are favorable, expect a push toward a Phase 2 expansion with refined eligibility and potentially combination strategies. If the biodistribution signal is inconsistent or marrow exposure rises with dose, the program may have to revisit dosing schema, fractionation, or companion diagnostics before it can challenge the PSMA standard.
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.
