Phase 1 study launches of anti-KLK3 monoclonal antibody for advanced prostate cancer

A first-in-human phase 1 clinical trial has begun evaluating RAD 402, an anti-KLK3 monoclonal antibody radiolabeled with terbium-161 (Tb161), in patients with advanced prostate cancer, Radiopharm Theranostics announced.¹

According to the company, “Targeting KLK3 and leveraging the dual emission of Tb161 represents an innovative approach for radiotherapies in prostate cancer.”

KLK3 encodes prostate-specific antigen (PSA). The KLK3 gene is highly expressed in prostate cancer cells, with limited expression outside of the prostate. Preclinical data on RAD 402 in mouse xenografts suggested strong tumor uptake with limited bone marrow involvement and hepatic clearance consistent with monoclonal antibody pharmacokinetics.

“Dosing the first patient in our phase 1 study of RAD 402 marks an important step forward for Radiopharm and for patients with advanced prostate cancer,” said Riccardo Canevari, CEO and Managing Director of Radiopharm Theranostics, in the news release.¹ “RAD 402 is a differentiated, first-in-class, next-generation radiotherapeutic designed to selectively target KLK3-expressing tumors while minimizing off-target exposure. With preclinical data demonstrating strong tumor uptake and minimal bone or marrow involvement, we are optimistic about its potential clinical profile. Advancing this program into the clinic reflects our continued commitment to delivering meaningful data across our portfolio this year. I’d like to take the opportunity to thank our partners, TerThera and Cyclotek, for the great support in supplying Tb161, radiolabeling, and distributing RAD 402.”

The phase 1 study (NCT07259213) is evaluating the safety, tolerability, whole-body distribution, and preliminary clinical activity of RAD 402 in patients with locally advanced or metastatic castration-resistant prostate cancer. The investigators plan to enroll approximately 73 patients in Australia. To be eligible for enrollment, patients must be at least 18 years of age and have a documented history of disease progression during or after their most recent line of anticancer therapy.

The study will be conducted in 2 phases. In the first phase, patients will receive escalating doses of RAD 402 to determine the maximum tolerated dose and/or recommended phase 2 dose (RP2D) for expansion. In the second phase, participants will receive RAD 402 at the RP2D to further characterize the safety and preliminary efficacy of the agent.

The primary outcome measures for the study include the incidence of treatment-emergent adverse events, the RP2D of RAD 402, and the agent’s preliminary antitumor activity, as measured by biochemical response to treatment. The investigators will also assess the pharmacokinetics, radiation dosimetry, and biodistribution of RAD 402.

Radiopharm Theranostics noted that data from the first 2 dose levels will be shared in the second half of 2026. Final completion of the study is expected in March 2029.²

REFERENCES

1. Radiopharm Theranostics doses first patient in phase 1 clinical study of RAD 402 in advanced prostate cancer. News release. Radiopharm Theranostics. March 27, 2026. Accessed March 30, 2026. https://www.globenewswire.com/news-release/2026/03/27/3263666/0/en/Radiopharm-Theranostics-Doses-First-Patient-in-Phase-1-Clinical-Study-of-RAD-402-in-Advanced-Prostate-Cancer.html

2. A Study of Terbium 161 (161Tb)-RAD402 in Participants With CRPC (RAD402). ClinicalTrials.gov. Last updated March 12, 2026. Accessed March 30, 2026. https://clinicaltrials.gov/study/NCT07259213