Phase 1 Trial for RAD 402, Terbium Based Radioligand for Metastatic or Locally Advanced or Prostate Cancer

Australian Human Research Ethics Committee has approved the initiation of a first‑in‑human Phase 1 therapeutic trial of RAD 402, a KLK3 (PSA)‑targeting monoclonal antibody labeled with terbium‑161 for patients with metastatic or locally advanced prostate cancer. The approval positions the program to begin site activation and enrollment in Australia, marking a notable milestone for a radiotherapeutic that pairs a prostate‑specific target with an isotope designed to intensify sub‑cellular energy deposition in tumors.​

RAD 402 is a humanized IgG1 antibody engineered to bind KLK3 with high affinity and undergo internalization in prostate cells, a profile intended to shuttle its radionuclide payload into tumor tissue while limiting exposure to non‑target organs. The target, KLK3, the gene encoding Prostate Specific Antigen, is abundantly expressed in prostate tissue and in most prostate adenocarcinomas, including their metastases, offering a biologic rationale for a prostate‑selective radiotherapeutic approach.​

The choice of terbium‑161 is central to the program’s thesis: unlike beta‑only emitters, 161Tb delivers both medium‑energy beta particles and low‑energy Auger and internal conversion electrons, concentrating lethal dose over nanometer‑to‑micrometer ranges that may be advantageous against micrometastases and isolated cancer cells while sparing surrounding tissue. Company statements explicitly point to this dual‑emission profile as a driver of anticipated antitumor activity and as a reason to advance the agent into human testing now cleared by ethics approval.​

Preclinical biodistribution in mouse xenograft models demonstrated strong and selective tumor uptake of RAD 402 with limited bone and marrow uptake and a hepatic excretion pattern consistent with monoclonal antibodies, supporting clinical translation into first‑in‑human evaluation.

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