Blue Earth Therapeutics starts Phase 2 trial for Lutetium (177Lu) rhPSMA-10.1 in metastatic castration-resistant prostate cancer

Blue Earth Therapeutics, based in Oxford, UK, announced significant progress in the development of their innovative radioligand therapy for prostate cancer. On May 1, 2025, the company began enrolling patients in a Phase 2 clinical trial to assess their radiohybrid, lutetium-labelled, PSMA-targeted investigational treatment. This study primarily aims to evaluate the treatment's efficacy by measuring the percentage of patients who experience a reduction of at least 50% in Prostate-Specific Antigen (PSA) levels. Additionally, it will assess radiographic progression-free survival and overall patient safety.

The clinical trial explores multiple dosing regimens that focus on delivering higher doses of radiation when the tumor burden is typically greatest, which is at the start of treatment. This approach diverges from previous radioligand therapy studies, which administered a consistent dose regardless of tumor burden. The study aligns with the US FDA's Project Optimus initiative, which encourages drug developers to optimize dosing early in a product's development to ensure an optimal benefit-risk profile.

To achieve this, the trial will implement innovative loading dose strategies. One strategy involves administering a higher dose during the first two treatment cycles, while another shortens the interval between the first three doses from six weeks to three weeks. The trial is also designed to evaluate the clinical benefits of administering high total doses of radioactivity, up to 60GBq. Phase 1 data demonstrated a favorable ratio of uptake in tumor tissues compared to healthy tissues such as kidneys and salivary glands.

David Gauden, DPhil, CEO of Blue Earth Therapeutics, emphasized the importance of this advancement in the development of the Lutetium (177Lu) rhPSMA-10.1 injection. He noted that commencing treatment at the full intended therapeutic dosing levels provides an excellent opportunity to assess the therapy's benefits for patients. With up to 20 sites enrolling participants, Blue Earth Therapeutics anticipates obtaining the first study results early next year. Gauden expressed gratitude to the physicians and patients at Biogenix Molecular in Florida for recruiting the first trial participants.

Prostate cancer remains a significant health challenge, with an estimated 50,055 new cases of metastatic prostate cancer expected in the United States in 2025. Despite a decline in prostate cancer death rates over the past three decades, the five-year survival rate for newly diagnosed metastatic cases remains low at 36.6%, highlighting the urgent need for improved patient outcomes.

Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) compounds are key to this treatment approach. These compounds feature a PSMA-targeted receptor ligand connected to two labeling moieties, allowing for radiolabeling with diagnostic isotopes like 18F or 68Ga for PET imaging, or therapeutic isotopes like 177Lu or 225Ac for radioligand therapy. This versatile design offers potential targeted treatment options for prostate cancer patients and originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive worldwide rights to the rhPSMA diagnostic imaging technology in 2018 and therapeutic rights in 2020, subsequently sublicensing the therapeutic application to its sister company, Blue Earth Therapeutics.

Blue Earth Therapeutics, a clinical-stage company within the Bracco family of companies, is committed to advancing next-generation targeted radiotherapeutics for cancer treatment. The company has attracted additional investors, raising $76.5M in a Series A financing round in 2024. With expertise in radiopharmaceutical and oncology drug development, Blue Earth Therapeutics aims to innovate and enhance current technologies and rapidly introduce new targeted therapies for serious diseases. Their initial focus is on prostate cancer, with an emerging pipeline of promising treatments.